Interventional therapies for chronic pain

INTRODUCTION — For some patients with chronic pain who do not obtain satisfactory analgesia with conventional first line approaches, interventional therapy may provide a safe and effective option. Interventional therapy refers to a group of invasive analgesic techniques including injections, ablations, infusion therapies, neuromodulation, and some minimally invasive surgical techniques.

This topic will discuss some of the most commonly used interventional procedures, including contraindications, description of the procedure itself, and, if noted, potential complications. Where indicated below, the indications for procedures and the role in therapy for specific conditions is discussed in separate UpToDate topics on those conditions.

PATIENTS WITH ALTERED COAGULATION — Patients with coagulopathy, who are taking anticoagulant or antiplatelet medications, or with severe thrombocytopenia, may be at increased risk of bleeding with interventional procedures. The degree of risk and the potential consequences if bleeding occurs vary depending on the site of the procedure and the ability to identify and compress bleeding. Decisions regarding holding anticoagulants and/or performing interventional procedures in patients with thrombocytopenia should be made on an individual basis. For patients taking anticoagulants, there should be a risk/benefit analysis that includes the reason the patient is taking the anticoagulant. These decisions may require collaboration among the interventionalist, the referring clinician, and the patient.

Pain medicine societies have created guidelines that assign a level of bleeding risk to various interventional procedures, and have made recommendations on the timing of procedures relative to doses of medications that affect coagulation, to minimize the risk of bleeding (table 1) [1].

SPINE PROCEDURES

Epidural glucocorticoid injection — Epidural glucocorticoid injections (also known as epidural steroid injections [ESI]) are used to treat back pain that may be refractory to conservative management. The most common condition treated is radicular pain, however this procedure may be used for spinal stenosis with or without neurogenic claudication, and chronic low back pain. Indications for these injections and evidence of efficacy are discussed separately. (See "Subacute and chronic low back pain: Nonsurgical interventional treatment", section on 'Glucocorticoid and other injections'.)

Contraindications — Epidural glucocorticoid injection is strictly contraindicated in patients with infection at the injection site, systemic infection, or coagulopathy.

Procedure — The procedure is typically performed prone, with fluoroscopy, and with local anesthesia. The use of sedation varies among institutions, ranging from no sedation to deep sedation, and may include the use of monitored anesthesia care. (See "Monitored anesthesia care in adults".)

Epidural glucocorticoid injection is performed by injecting the drug through a needle tip placed in the epidural space, between the dura and the ligamentum flavum (figure 1). The needle can be inserted via a translaminar approach (through the interlaminar space in the spine), the transforaminal approach (more lateral through the neuroforamen dorsal to the nerve root), or the caudal approach (from the sacrum just above the coccyx through the sacral hiatus and sacral canal) (figure 2). A catheter may be used in the interlaminar or the caudal approach if needed to obtain optimal spread of the injected solution to the desired location. If fluoroscopy is used, contrast dye is usually injected to confirm placement of the needle and injectate in the epidural space.

The injected solution contains glucocorticoid with or without local anesthetic. We inform patients that they may not appreciate benefits from the epidural glucocorticoid injection for 24 to 72 hours or even later, whether or not local anesthetic is used. This varies greatly as some patients feel relatively immediate relief (particularly if local anesthetic is used) and others may not feel substantial benefits until days or weeks later. This variation may be because the injected glucocorticoid has both direct effects in the spine and also systemic effects.

As an outpatient/ambulatory procedure, the patient can usually go home after a brief period of post-procedure observation. We follow up at approximately four weeks. If there is no benefit at this time, we consider alternative treatments and approaches. If there is an incremental benefit we may repeat the procedure based on the patient tolerance for exposure to additional glucocorticoid. If the patient has complete or near complete relief, we typically will observe and re-evaluate if pain returns. In most well selected patients, pain relief lasts for at least two months.

Complications and adverse events — Serious complications of epidural glucocorticoid injection are rare. Efficacy, complications and adverse events are discussed separately. (See "Subacute and chronic low back pain: Nonsurgical interventional treatment", section on 'Adverse events'.)

There are potential adverse effects from systemic absorption of the glucocorticoid, including elevated blood glucose, hypertension, and mood changes. Frequent injections and higher doses of glucocorticoids can cause decreased bone density. At our institution, we use triamcinolone 40 mg or dexamethasone 10 mg per injection, with a frequency of not more than every six weeks to three months and a maximum of four injections over 12 months. At these doses and intervals, the risk of decreased bone density is low. (See "Major adverse effects of systemic glucocorticoids".)

Kyphoplasty and vertebroplasty — These vertebral augmentation procedures are used to treat vertebral compression fractures due to osteoporosis, metastatic bone disease, lymphoma, or multiple myeloma. Both vertebroplasty and kyphoplasty involve injection of bone cement into the collapsed vertebra; kyphoplasty also involves insertion of inflatable bone tamps to create a cavity for the cement. These procedures are discussed in detail separately. (See "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment", section on 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)'.)

Medial branch block and ablation — The medial branch nerves are branches of the spinal dorsal rami. They innervate the facet joints of the spine, and run along the transverse process lateral to the facet joint (figure 3) [2]. Medial branch blocks may be used to help diagnose pain from facet joints (zygapophyseal joints), and as a predictive test in anticipation of potential radiofrequency ablation of the medial branch nerves that innervate the facet joints. Medial branch blocks may be performed for suspected cervical or lumbar facet joint related pain. They have also been used for pain from vertebral compression fracture [3].

●Procedure – Medial branch block is typically performed prone, with fluoroscopy, and with local anesthesia. The use of sedation varies among institutions, ranging from no sedation to deep sedation, and may include the use of monitored anesthesia care (see "Monitored anesthesia care in adults"). This is an outpatient procedure and the patient can typically be discharged after a very brief period of observation.

Under fluoroscopic guidance, local anesthetic is injected at the junction of the superior articular process and the transverse process.

Post-procedure pain is usually mild and manageable with over-the-counter analgesics and icing.

A successful block would result in at least 80 percent improvement in pain. Many insurance policies, including Medicare in many regions, require two successful medial branch blocks on different days in order to cover radiofrequency neurotomy (RFN), the definitive procedure. Once MBB is complete, the patient can then be brought back as soon as the next day for the RFN. (See 'Radiofrequency neurotomy (radiofrequency ablation)' below.)

●Complications – Complications are rare and like other nerve blocks, may include pain, bleeding, infection, and injury of nearby structures. (See "Overview of peripheral nerve blocks", section on 'Complications'.)

Intra-articular facet joint injection — Intra-articular facet (IAF) joint injection may be performed for patients who are strongly suspected of having facet related spinal pain, particularly for those who may be too young for, or otherwise unable or unwilling to undergo, RFN of medial branches. Ablation of the medial branches destroys the nerves, but they usually grow back over time, and may grow back faster in healthy young individuals, such that they would need more years of repeat RFN if necessary than older patients. In individuals less than 40 to 50 years of age, an IAF injection may be tried instead. IAF injections may be diagnostic (confirming facet joint pain) with local anesthetic (LA) injection, or therapeutic with glucocorticoid injection with or without LA, and can help determine whether to consider RFN. (See 'Radiofrequency neurotomy (radiofrequency ablation)' below.)

IAF injections may be performed in the lumbar, cervical, or thoracic regions, however, risks are higher with cervical and thoracic injections [4] and they are much more rarely performed.

Diagnostic blocks are performed more than once, typically using local anesthetics with different duration of action, to minimize the risk of false positive results. A successful block provides at least 50 percent pain relief for the duration of the local anesthetic.

●Procedure – The procedure is performed using local anesthesia with or without sedation, as an outpatient procedure. Under fluoroscopic guidance, a needle is inserted into the facet joint, and local anesthetic is injected (figure 3). For therapeutic block, glucocorticoid is added to the injectate.

●Adverse events and complications – Adverse events are rare and may include pain, bleeding, infection, and injury of nearby structures [4-6]. Major complications are extremely rare. In a single institution retrospective review of approximately 12,000 IAFs, procedure related major adverse events requiring hospitalization or a visit to the emergency department occurred in 0.07 percent of injections [5]. All major complications were infections. In another single institution observational study of 43,000 blocks, there were no major complications [4].

Complications specific to cervical IAF include vertebral artery damage or injection and phrenic nerve palsy [7].

Others — Other spine procedures that are not widely used include intradiscal injection and vertebral RFN.

SYMPATHETIC BLOCKS AND NEUROLYSIS — Blockade of the sympathetic nervous system may be considered when pain is potentially mediated or amplified by aberrant sympathetic activity, thought to be related to shared pathways between nerves carrying pain signal and autonomic fibers. Symptoms may be diffused and seem out of proportion to pain expected based on normal somatic anatomy (eg, usual dermatomal pattern or distribution). (See "Complex regional pain syndrome in adults: Pathogenesis, clinical manifestations, and diagnosis".)

In addition to pain relief, sympathetic blocks can be used to improve perfusion, and have been used for lower extremity ischemia and coronary perfusion [8,9]. (See "Treatment of Raynaud phenomenon: Refractory or progressive ischemia", section on 'Limited role of proximal sympathectomy'.)

Anatomy — Sympathetic axons exit their nuclei in the spinal cord at the T1 to L2 or L3 levels and continue to form paravertebral or prevertebral ganglia. Paravertebral ganglia comprise the sympathetic trunk along the vertebral column, and join at the level of the coccyx to create the ganglion impar. Prevertebral ganglia exist in the preaortic celiac, superior mesenteric and inferior mesenteric plexuses. Both efferent sympathetic fibers and afferents from internal organs traverse the sympathetic ganglia.

In the cervical and lumbar regions, sympathetic ganglia and plexuses are separate from somatic nerves, such that sympathetic blocks can achieve analgesia without somatic sensory block. This is not true in the thoracic region, where injecting near the paravertebral chain is less common and has heightened risks due to proximity of somatic nerves, neuraxial structures, and the pleura.

Contraindications — Sympathetic blocks are contraindicated in patients with infection at the injection site or systemic infection. These blocks are considered intermediate risk blocks due to concerns of bleeding. Thus, the risk of bleeding should be balanced against the potential benefit, which may be a particular issue for patients with intractable pain near the end of life.

Block sites and indications — Sympathetic blocks and neurolysis may be performed in well-chosen cases for ischemic or sympathetically mediated pain, including neuropathic pain (eg, painful diabetic neuropathy, phantom limb pain, postherpetic neuralgia), complex regional pain syndrome, and chronic abdominal, pelvic or perineal pain. Neurolytic blocks are most commonly used for intractable visceral cancer pain, particularly for pancreatic cancer. The role of sympathetic blocks for patients with pancreatic cancer is discussed separately. (See "Supportive care for locally advanced or metastatic exocrine pancreatic cancer", section on 'Sympathetic neurolytic blocks'.)

The most common sites for sympathetic blocks are described here. Though some of these structures are not composed solely of sympathetic fibers, it is believed that the lasting relief occurs from blocking transmission of the sympathetic signals [10,11]. In some cases, a diagnostic local anesthesia block may be performed prior to ablation at these sites. Efficacy of a diagnostic sympathetic block should be clear within minutes of injection as evidenced by appropriate changes in blood flow, limb temperature and color, or other relevant transient autonomic signs such as a temporary Horner syndrome (ie, conjunctival injection, miosis and ptosis). (See "Horner syndrome".)

●Stellate ganglion – The stellate ganglion is located just anterior to the transverse process of C7. It provides sympathetic fibers to the anterior rami of C7, C8, and T1 and brachial plexus, and visceral branches to the inferior cardiac nerve and cardiac plexus. The stellate ganglion block may be used for sympathetically mediated conditions of the head, neck, upper chest, and upper extremities. (See "Complex regional pain syndrome in adults: Treatment, prognosis, and prevention", section on 'Sympathetic nerve blocks'.)

Stellate ganglion blocks can be used for chronic medical conditions including angina, ventricular arrhythmias, and posttraumatic stress disorder. While the vasodilatory effects may explain the improvement of angina, it is unclear how these blocks improve ventricular arrhythmias. (See "Electrical storm and incessant ventricular tachycardia", section on 'Management of refractory cases'.)

●Celiac plexus – The celiac plexus is formed by the greater, lesser, and least splanchnic nerves. It is located around the celiac artery and the root of the superior mesenteric artery. This plexus can be blocked at the level of T12 to L1 [12]. While celiac plexus blockade is most commonly performed for pain related to pancreatic cancer, it can also be used for pain involving other upper abdominal structures (eg, stomach, small intestine, or liver).

●Lumbar sympathetic chain – The lumbar sympathetic chain is located anterior to T1 to L2 or L3. Lumbar sympathetic blocks can be used for lower extremity pain (eg, from complex regional pain syndrome or vascular insufficiency). (See "Complex regional pain syndrome in adults: Treatment, prognosis, and prevention", section on 'Sympathetic nerve blocks'.)

●Superior hypogastric plexus – The hypogastric plexus consists of lumbar and pelvic splanchnic nerves, the abdominal aortic plexus, and the hypogastric nerves. It can be blocked with an injection at the anterior aspect of the L5 vertebral body level. It is used to treat pain of lower abdominal and pelvic structures [13].

●Ganglion impar – The ganglion impar is located on the anterior surface of the sacrum. It can be blocked at the sacrococcygeal junction to provide pain relief of the lower pelvis, perineum, and coccyx. (See "Coccydynia (coccygodynia)", section on 'Local injection'.)

Technique

●Imaging – Sympathetic blocks can be performed percutaneously with fluoroscopy, ultrasound, or computed tomography guidance. Celiac plexus block may also be performed during upper gastrointestinal endoscopy. Most intra-abdominal blocks may also be performed during surgical procedures.

●Positioning and monitoring – Patient positioning depends on the procedure. In our program, patients are positioned prone for celiac plexus, lumbar sympathetic, and ganglion impar blocks. Stellate ganglion blocks are performed with the patient supine.

Vital signs, level of sedation, and comfort are monitored throughout the procedure. The use of sedation varies among clinicians and also by patient preference or needs. Sedation ranges from minimal or light sedation (eg, low dose midazolam with or without fentanyl) to deep sedation with the use of monitored anesthesia care. We usually use minimal to moderate sedation, recognizing that the deeper sedation increases procedural risk.

●Drug choice – Blockade is initially performed with local anesthetic (eg, lidocaine or bupivacaine), with or without other medications (eg, glucocorticoids [betamethasone, triamcinolone, or dexamethasone] and botulinum toxin [14,15]). If neurolytic block is desired, often for patients at the end of life, chemical neurolysis can be performed, as discussed below. (See 'Chemical neurolysis' below.)

Thermal radiofrequency or pulsed radiofrequency can also be used for a prolonged effect. (See 'Radiofrequency neurotomy (radiofrequency ablation)' below.)

●Post-procedure monitoring – After the procedure, patients are assessed for signs of a successful sympathectomy, and the patient's self-report of pain relief. A successful sympathetic block is indicated by vasodilation causing erythema and temperature increases in the affected extremity. Successful stellate ganglion block may cause a temporary ipsilateral Horner syndrome (ie, conjunctival injection, miosis and ptosis). (See "Horner syndrome".)

Patients who undergo celiac plexus block should be monitored for hypotension and diarrhea after the procedure. In our clinic, patients who have had uncomplicated procedures and are stable are usually observed for approximately one hour, whereas longer monitoring may be required for those with any hemodynamic instability. Most patients are ultimately discharged to home.

Pain is minimal after most blocks and is manageable with over-the-counter analgesics.

●Monitoring block effect after discharge – Patients are often asked to keep a pain diary to assess block effect. If the procedure was diagnostic and will be used to determine whether a neurolytic or ablative sympathetic block will be performed, the degree of pain relief within the duration of action of the local anesthetic used for the block should be determined.

Side effects and complications — Sympathetic blocks are generally safe, and serious complications are very rare. Like other injections, they can cause bleeding, infection, or injury to nerves or other anatomic structures, depending on the site of injection.

Stellate ganglion or lumbar sympathetic injections may result in severe complications from inadvertent arterial injection of local anesthetic or spinal cord injury or infarction [10].

Side effects and complications associated with the sympathectomy reflect the predominance of parasympathetic effect. They include Horner syndrome after stellate ganglion block, and diarrhea and hypotension after celiac plexus block [10]. Other complications include orthostatic hypotension and bowel/bladder dysfunction.

Efficacy

●Efficacy of blocks – There is little literature on the efficacy for stellate ganglion blocks, mostly limited to small case series or case reports. Efficacy for complex regional pain syndrome (CRPS) and for ventricular arrhythmias is discussed separately. (See "Complex regional pain syndrome in adults: Treatment, prognosis, and prevention", section on 'Sympathetic nerve blocks' and "Electrical storm and incessant ventricular tachycardia", section on 'Management of refractory cases'.)

A number of mostly small or retrospective studies have reported effective pain relief from superior hypogastric plexus blocks in up to 70 percent of patients with refractory pain due to endometriosis [16,17]. As an example, in a retrospective single institution study of 76 ganglion impar blocks or neuroablations in 43 patients, for a variety of indications, 44 percent had sufficient pain relief after a block to avoid the need for neuroablation [17]. Overall, including patients who underwent neuroablation, 91 percent had pain reduced by ≥50 percent, and 37 percent had pain reduced by ≥80 percent, sustained at four month follow up. Use of ganglion impar blocks for coccydynia is discussed separately. (See "Coccydynia (coccygodynia)", section on 'Local injection'.)

●Efficacy of sympathetic neurolysis – Radiofrequency neurotomy (RFN) provides more sustained analgesia in the range of months to years, as an alternative to local anesthetic sympathetic blockade. RFN is discussed below. (See 'Radiofrequency neurotomy (radiofrequency ablation)' below.)

Multiple studies have demonstrated efficacy of celiac plexus neurolysis for pancreatic cancer pain and pancreatitis, which are discussed separately. (See "Supportive care for locally advanced or metastatic exocrine pancreatic cancer", section on 'Sympathetic neurolytic blocks' and "Endoscopic ultrasound-guided celiac plexus interventions for pain related to pancreatic disease", section on 'Efficacy' and "Chronic pancreatitis: Management", section on 'Celiac plexus block'.)

Superior hypogastric plexus neurolysis may be used for visceral pelvic pain that is refractory to medical management [18-20]. In a single institution retrospective study of 180 patients with pelvic cancer pain who underwent superior hypogastric plexus chemolysis with phenol, approximately 50 percent of patients had over 50 percent reduction in pain scores at 6 months after the injection [19]. Daily morphine milligram equivalent requirement was reduced for the first three months, compared with opioid use prior to the injection.

NEUROLYTIC PROCEDURES — Neurolytic procedures produce analgesia by destroying afferent neural pathways or sympathetic ganglia involved in pain transmission [21,22].

Mechanisms — For neurolytic procedures nerve tissue can be destroyed with heat (thermal radiofrequency) or by injecting neurolytic substances (water, hypertonic saline, glycerin, phenol, or alcohol) [23]. All neurolytic techniques result in Wallerian degeneration (ie, degeneration of the nerve axon distal to the destructive lesion) to some degree. However, if the axolemma is intact, nerve regeneration occurs, leading to a return of sensation in approximately three to six months.

Choice of technique — The technique is chosen based on the indication and the desired duration of effect. The extent of nerve regeneration and the extent and time course of recovery affect the choice of technique.

●Thermal ablation is associated with lower risks of complications than chemical ablation but often provides less sustained benefits as the nerves regenerate.

●Chemical neurolysis with alcohol or phenol dehydrate neural tissue and cause necrosis and demyelination in addition to Wallerian degeneration, such that the effects last longer. These agents are more commonly used in end-of-life care since there can be a heightened risk of deafferentation pain.

Indications for neurolytic blocks and procedures — Both somatic and sympathetic neurolytic blocks and procedures may be performed for various conditions. Neurolytic blocks should only be considered when more conservative therapies have failed.

Neurolysis is most commonly performed for cancer patients with advanced disease or for those with intractable pain unresponsive to more conservative therapies [24,25]. (See "Supportive care for locally advanced or metastatic exocrine pancreatic cancer", section on 'Sympathetic neurolytic blocks'.)

Radiofrequency neurotomy (RFN) and chemical neurolysis have also been performed for chronic non-cancer pain, including facet joint pain (medial branch neurolysis), chronic shoulder, knee, and hip pain [26], and trigeminal neuralgia. (See "Trigeminal neuralgia", section on 'Surgical techniques'.)

Radiofrequency neurotomy (radiofrequency ablation) — RFN (also called radiofrequency ablation [RFA]) uses radio waves to heat a small area of nerve tissue to destroy it. One type of device (cooled radiofrequency [RF]) used for medial branch RFN circulates cool water through the probe and creates a larger lesion than conventional RFN.

Contraindications — RF procedures are contraindicated in patients with infection at the injection site or systemic infection. Relative contraindications include fracture, overlying tumors/masses/hardware, radiculopathy, infection, and coagulopathy [27-30].

The risk of serious bleeding varies depending on the target structure. As examples, cervical medial branch RFN is considered an intermediate risk procedure, and lumbar medial branch RFN would be considered a low risk procedure. Most peripheral nerve RFN procedures would be considered low risk.

Indications — The most common indications for RFN are axial neck or back pain when the facet joints have been identified as the etiology of pain (eg, non-radicular axial spine pain with possible paraspinal tenderness in the location of the facet joints) [27-30]. Other indications include knee, hip, or sacroiliac joint pain that may be from degenerative changes such as osteoarthritis [31]. The targets for the knee, hip, and sacroiliac joints, respectively, are the genicular articular nerves of the knee, articular branches of the femoral and obturator nerves in the hip, and the sacral lateral branch nerves for the sacroiliac joint. Since the ablated nerves can regenerate, a patient who has responded to a prior ablation may be eligible for a repeat ablation/neurotomy of the same targets at a later time [32-35].

Indications for sympathetic neurolysis are discussed above. (See 'Block sites and indications' above.)

Technique — A diagnostic block with local anesthetic may be performed prior to an RFN procedure [36-38]. The RFN procedure can be performed as soon as the next day after a successful block.

Patient positioning varies depending on the target nerve. RFA is performed by inserting a specialized needle through the skin, using fluoroscopy or ultrasound guidance to place the needle tip in close proximity to the target nerve, after which the lesion is created [27,28,31]. As an example, in the lumbar region a 90 second 80^o C lesion is created to coagulate nerve tissue.

RFN is usually an outpatient procedure, performed with local anesthesia, with or without sedation. The procedure takes 15 to 30 minutes, and the patient can usually be discharged following a brief recovery period. Post-procedure pain is managed with over-the-counter analgesics.

Efficacy — Efficacy of neurolytic procedures and the potential for adverse effects vary widely based on the speed with which the individual’s nerves regenerate and whether regeneration results in normal neural function, acute neuritis, or chronic aberrant sensory changes. (See 'Complications' below.)

Various studies, including randomized controlled trials, have found that RFA procedures may be highly effective for pain relief [27-30]. As an example, reported rates of positive outcome (ie, >50 percent pain relief at more than three months) are seen in more than 65 percent in patients who had effective diagnostic blocks prior to RFA [38]. If pain recurs, repeat RFA can be performed. Studies have found that repeat medial branch RFA was successful in up to 65 to 90 percent of patients after an initially successful block [33-35].

Chemical neurolysis — Chemical neurolysis is performed similarly to RFN; instead of using an RF probe, a needle is inserted and phenol, glycerol, or alcohol is injected. In our practice, phenol is used most commonly, and often comes in a viscous formulation, which can help limit its spread to surrounding tissues [39]. Alcohol is an irritant and can cause pain on injection [40]. Another agent used for chemical neurolysis is glycerol, which is more commonly used for Gasserian ganglion rhizolysis in the trigeminal nerve pathways [39].

In studies of treatment of trigeminal neuralgia, chemoneurolysis has been effective for up to five years with results comparable to microvascular decompression [41]. Glycerol injection of the Gasserian ganglion also results in a similarly long duration of activity in approximately 50 percent of patients, with low risk of adverse effects [42].

Complications — Complications of RFN are rare, and include infection, bleeding, injury to surrounding anatomic structures (eg, nontarget nerves, blood vessels, organs), motor paresis, anesthesia dolorosa (ie, pain superimposed in an area that lacks or has impaired sensation), and motor paresis.

Other possible complications include acute neuritis and chronic aberrant sensory changes. The incidences of these outcomes are not well established. Adverse outcomes are thought to be more common when larger and more complex nerves are ablated (ie, larger sensory fibers or mixed sensory and motor fibers, or in younger or healthier individuals who may have more robust regenerative mechanisms).

Postneurotomy neuritis is a transient, localized, burning, neuropathic pain that has been specifically described after RFN. Based on limited data, the incidence is estimated between 0.5 and 7 percent, and most cases last approximately two weeks or longer [43,44].

Historically, neurolytic interventions have been thought to potentially carry the risk of producing a new "deafferentation pain," due to axonal sprouting and neural regeneration. In our practice, this is a rare outcome but the exact incidence of deafferentation pain is unknown. Methods that preserve neural architecture (ie, RFN) and allow for regeneration are less likely to be followed by neuritis or a deafferentation pain syndrome. Deafferentation often presents similarly to chronic neuropathic pain, characterized by dysregulated sensory function and associated allodynia, hyperesthesia and hyperpathia, as well as other forms of abnormal local sudomotor and temperature changes. Once a deafferentation pain syndrome develops, it can be difficult to treat.

NEUROMODULATION — Neuromodulation in the context of pain management refers to the application of electrical stimulation to nerves to alter (modulate) pain signaling. Neuromodulation is increasingly used for pain management and neuromodulation technology is rapidly evolving. The most commonly used techniques are discussed here and appear in a table (table 2).

Spinal cord stimulation — Spinal cord stimulation (SCS) is a neuromodulation technique used to treat neuropathic and sympathetically mediated chronic pain. SCS involves percutaneous or surgical implantation of electrodes in the epidural space, with power supplied by an implanted pulse generator (battery). Indications, efficacy, placement technique, and complications are discussed separately. (See "Spinal cord stimulation: Placement and management".)

Dorsal root ganglion stimulation — Dorsal root ganglion (DRG) stimulation involves inserting leads via the epidural space into the neuroforamen where the spinal nerve roots and DRG exit the neuraxis. The DRG is a collection of sensory cell bodies that lies within the epidural space, surrounded by a minimal amount of cerebrospinal fluid. Thus, stimulation requires very low electrical current, lower than the current required for spinal cord stimulation [45].

The indications for DRG stimulators are evolving. DRG stimulation is used for focal neuropathic pain syndromes, with the strongest evidence of benefit for lower extremity complex regional pain syndrome (CRPS), and limited evidence for use in diabetic and other peripheral neuropathies [45]. In a randomized trial that compared DRG versus spinal cord stimulator placement in patients with lower extremity CRPS or causalgia, pain relief ≥50 percent at three months was achieved in 81 percent of patients who had permanent DRG implants, compared with 56 percent who had SCS implants [46]. Results were similar at 12 month follow-up. (See "Complex regional pain syndrome in adults: Treatment, prognosis, and prevention", section on 'Dorsal root ganglia stimulation'.)

The procedure is very similar to spinal cord stimulator placement, which is described in detail separately. Contraindications are also similar. (See "Spinal cord stimulation: Placement and management".)

Peripheral nerve stimulation — Peripheral nerve stimulation is an evolving field within neuromodulation and pain medicine, advanced by availability of compact, minimally invasive percutaneous systems [47]. Nerve targets range from suprascapular and axillary nerves in the upper extremity for shoulder pain [48] and femoral/sciatic nerves in the lower extremity for amputation-related pain [49,50]. Most peripheral nerve stimulator leads can be precisely placed with ultrasound guidance, with local anesthesia and minimal sedation. These procedures are similar to placement of continuous peripheral nerve block catheters, which are described in UpToDate topics on individual blocks. (See "Overview of peripheral nerve blocks", section on 'Continuous catheter techniques'.)

Stimulators may be placed for temporary use (eg, for postoperative pain), and may also be placed permanently, often after a trial. In one randomized trial including 94 patients with severe chronic postsurgical or posttraumatic pain of peripheral nerve origin who were implanted with a peripheral nerve stimulator lead, pain reduction of ≥30 percent at three months was greater in patients who had stimulation compared with those who did not (27.2 versus 2.3 percent) [47]. No serious device related adverse events occurred.

For most sites, peripheral nerve stimulator placement is considered a low risk procedure for serious bleeding [1]. Thus, it may be unnecessary to stop anticoagulants or antiplatelet medications or time the procedure based on dosing of those medications, and peripheral nerve stimulators may be better options than neuraxial stimulation for patients with coagulopathy.

Noninvasive transcutaneous devices — Transcutaneous electrical nerve stimulation (TENS) has long been used to treat various conditions, including myofascial, low back, and osteoarthritic pain. The transcutaneous stimulators used to deliver TENS have evolved to treat other chronic pain conditions. Devices targeting the terminal branches of the trigeminal nerve (V1 distribution) have been used to treat acute and chronic migraine symptoms. Applied to the skin in the forehead area, the patient can use these devices on demand and without complicated programming [51]. Additionally, some devices target the vagus nerve in the cervical or auricular areas and have been used to treat headaches, including cluster and migraine variants, and chronic coronavirus disease 2019 (COVID-19) symptoms [52,53]. For most indications, evidence of efficacy of TENS is inconclusive. This is discussed separately. (See "Approach to the management of chronic non-cancer pain in adults", section on 'Transcutaneous electrical nerve stimulation (TENS)'.)

Complications and adverse events — Complications of all implanted devices include bleeding, infection, nerve injury, lead migration, pain at the site of the pulse generator, and equipment malfunction.

●Complications of SCS are discussed separately. (See "Spinal cord stimulation: Placement and management", section on 'Complications'.)

●Reported complication rates for DRG stimulators vary widely, but appear to be similar to SCS. As an example, in one retrospective study of safety reports using manufacturer records, safety events were reported in 3.2 percent of placements (based on 500 placements), and in 3.1 percent of SCS placements (based on 2000 placements) [54]. Infection accounted for one third of the reports. Neurologic complications are rare, usually transient, but potentially severe, including weakness, paralysis, and incontinence. Thus, guidelines from the American Society of Pain and Neuroscience recommend DRG placement with the patient awake and able to report radicular pain or paresthesia, or with intraoperative neurologic monitoring if general anesthesia is necessary [55].

●Because peripheral nerve stimulator leads are often placed at more mobile sites than SCS or DRG stimulators, lead migration and erosion are more significant concerns with peripheral stimulators.

●Transcutaneous devices are usually well tolerated, but may cause local discomfort or erythema at the application site. Stimulators placed in the head or neck for vagal or trigeminal nerve stimulators may cause dizziness [56].

INTRATHECAL THERAPY — Intrathecal therapy involves the use of a specialized implantable, programmable infusion pump to deliver analgesic medications and/or antispasmodics directly into the cerebral spinal fluid and the spinal cord. Intrathecal drug administration bypasses the blood brain barrier and achieves analgesia with much lower systemic levels of medications.

Indications — Intrathecal therapy may be used for patients with intractable pain and/or severe spastic disorders for whom systemic therapy is ineffective at doses with tolerable side effects. Intrathecal therapy is used for patients with intractable cancer pain, or pain and/or spasticity as a result of multiple sclerosis, spinal cord injury, amyotrophic lateral sclerosis, or cerebral palsy. It is most commonly done for palliative care for patients near the end of life. Intrathecal therapy is rarely necessary for patients with intractable cancer pain, but when used, it can markedly improve quality of life. It can be of particular benefit in patients with recurrent pelvic cancers or those with mesothelioma, who with adequate pain control can continue anti-neoplastic therapy.

Use of intrathecal therapy in specific conditions is discussed separately, as follows.

●(See "Symptom management of multiple sclerosis in adults", section on 'Spasticity'.)

●(See "Chronic complications of spinal cord injury and disease", section on 'Intrathecal baclofen'.)

●(See "Symptom-based management of amyotrophic lateral sclerosis", section on 'Spasticity'.)

●(See "Cerebral palsy: Treatment of spasticity, dystonia, and associated orthopedic issues", section on 'Intrathecal baclofen'.)

Contraindications — Contraindications include infection at the insertion site, systemic infection and patient inability to tolerate the anesthetic necessary to place the device. For patients with coagulopathy (eg, related to advanced liver disease or cancer-associated disseminated intravascular coagulation), the risk of bleeding must be balanced against the benefit of excellent pain control.

The procedure may be ill advised in patients with severe cachexia and the risk of poor wound healing. Some pain specialists restrict use of intrathecal pumps to patients with life expectancy of at least three months, or occasionally two months in patients with intractable pain that is likely to respond to the pump.

Technique — An intrathecal trial is often performed to ensure that patients tolerate intrathecal medication and respond with a reduction in their pain. Trials can be performed in the office setting as a single intrathecal injection with morphine (most common) or as an inpatient infusion over several days [57]. In some institutions an inpatient trial is performed with epidural infusion instead of intrathecal infusion.

However, there is controversy over whether a trial is necessary [58]. Some health insurance carriers require a trial of intrathecal therapy, while others do not offer coverage for such trials.

●Intrathecal catheter placement is considered a high risk procedure for serious bleeding. Therefore, patients who take antithrombotic or antiplatelet medications may be asked to hold or change dosing so the procedure can be performed according to the relevant guidelines [1].

●The permanent intrathecal catheter and pump are placed in the operating room with general anesthesia or with monitored anesthesia care with local anesthesia and sedation.

●The patient is typically placed in the lateral decubitus position. A needle is inserted through the skin as for lumbar puncture or spinal anesthesia, with the tip in the subarachnoid space. The catheter is inserted through the needle and guided using fluoroscopy to the desired spinal level, congruent with the location of the patient's pain.

●A reservoir pocket is created under the skin of the anterior abdomen, which will hold either a subcutaneous port (accessed percutaneously and used with an external pump) or a fully implanted infusion pump. A fully implanted pump is typically used for patients with a life expectancy of more than three to four months, whereas a port is often placed for patients near the end of life.

●The catheter is then tunneled under the skin and connected to the reservoir.

Pump and medications — Implanted pumps are programmable via Bluetooth, and some come with remote control devices that allow patients to self-administer programmed doses of medication.

Morphine is the only FDA approved opioid for intrathecal therapy. Despite this, medications frequently used include hydromorphone, bupivacaine, clonidine, baclofen, and ziconotide. Refill intervals are dependent on medication concentration, rate, and patient tolerance. In general, patients may require a pump refill every few weeks to several months.

A variety of medications can be used alone or in combination for intrathecal infusion, including opioids (ie, morphine, hydromorphone, fentanyl, sufentanil), ziconotide, bupivacaine, clonidine, and baclofen [59]. Recommended agents and doses appear in the 2017 Polyanalgesic Consensus Conference (PACC) report and are beyond the scope of this topic [60].

Cancer patients who require these pumps are usually on significant doses of systemic opioids. The doses of opioids must be adjusted over the five to seven days since it often takes time to achieve an optimal intrathecal medication and infusion dose rate. Collaboration with cancer pain management or palliative care clinicians with specific expertise in intrathecal pump placement and management is strongly advised during this transition. Patients and their families need to be aware of the titration process and supported with as needed systemic medications and counseling.

Complications — Complications of intrathecal therapy may include side effects of the opioid (eg, nausea, pruritus, urinary retention), pump or catheter malfunction, cerebrospinal fluid leak, infection, and bleeding. A 2007 systematic review found 10 older studies that reported complications of intrathecal therapy systems, placed primarily for failed back surgery syndrome [61]. Opioid side effects were reported in up to a third of patients, and hardware or catheter problems in up to 20 percent. In a systematic review of studies of the use of intrathecal drug delivery systems in patients with cancer pain, complications were not uniformly reported and included side effects of the infused drug as well as device = related complications [62]. The mean rate of infection (including surgical site and device infections and meningitis) was 2.8 percent and was similar in patients who had implanted and external pumps.

A study of 1000 reports in 2018 and 2019 from the Manufacturer and User Facility Device Experience (MAUDE) database found that the most commonly reported adverse events were infection/erosion (15.7 percent of reports), motor stall (2.4 percent), and adverse medication reactions (11.8 percent) [63].

Infection is reported in up to 3 percent of patients, with most at the site of the implanted pump [62,64]. Catheter tip granuloma has been reported with intrathecal opioid infusion, some of which have required surgery for decompression [65].

Efficacy — For many patients intrathecal therapy provides sustained improvement in pain [62,66-68]. As an example, in a meta-analysis of various types of studies of patients with intrathecal delivery systems for cancer pain, pain scores were reduced by a mean of 3.3/10 points at >6 months (6 studies) and mean opioid consumption was reduced by over 300 morphine milligram equivalents per day (13 studies) [62].

SOFT TISSUE AND JOINT INJECTIONS — Injections into soft tissue and joints are often performed to treat common chronic pain syndromes, such as myofascial pain or painful arthropathy. These injections are discussed in detail separately. (See "Intraarticular and soft tissue injections: What agent(s) to inject and how frequently?" and "Joint aspiration or injection in adults: Technique and indications".)

SUMMARY — Interventional procedures are described briefly here, with further details above.

●General issues

•These are typically outpatient procedures, performed with local anesthesia with or without sedation, with fluoroscopy or other imaging.

•Patients with coagulopathy, who are taking anticoagulant or antiplatelet medications, or with severe thrombocytopenia may be at increased risk of bleeding with interventional procedures. The degree of risk varies with the procedure. (See 'Patients with altered coagulation' above.)

•Serious complications are very rare. Complications specific to the procedures are discussed above.

●Spine procedures – These procedures are usually outpatient procedures performed with local anesthesia with or without sedation.

•Epidural glucocorticoid injection – This procedure is used to treat back pain refractory to conservative measures. It is performed by injecting glucocorticoid with or without local anesthetic through a needle placed in the epidural space. (See 'Epidural glucocorticoid injection' above.)

•Kyphoplasty and vertebroplasty – These procedures are used to treat vertebral compression fractures by injecting bone cement into the collapsed vertebra. (See 'Kyphoplasty and vertebroplasty' above and "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment", section on 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)'.)

•Medial branch blocks – These blocks are used to diagnose pain from facet joints, which are innervated by medial branches of the spinal dorsal rami. Local anesthetic is injected at the junction of the superior articular process and the transverse process. (See 'Medial branch block and ablation' above.)

•Intra-articular facet joint injection – These procedures are used for patients strongly suspected of having facet related spinal pain. Local anesthetic or glucocorticoid is injected directly into the joint. (See 'Intra-articular facet joint injection' above.)

●Sympathetic blocks and neurolysis – These blocks may be performed for ischemic or sympathetically mediated pain at the level of the stellate ganglion, celiac plexus, lumbar sympathetic chain, superior hypogastric plexus, or ganglion impar. They are performed percutaneously with imaging, or for celiac plexus block, during upper gastrointestinal endoscopic ultrasound. (See 'Sympathetic blocks and neurolysis' above.)

●Neurolytic procedures – Neurolytic procedures produce analgesia by destroying afferent neural pathways or sympathetic ganglia involved in pain transmission, and should only be considered when more conservative measures fail. They are performed with thermal ablation using radiofrequency neurotomy or with chemical neurolysis using alcohol, phenol, or glycerol. (See 'Neurolytic procedures' above.)

Pain can recur if nerves regenerate after neurolytic procedures. There are also risks of postneurotomy neuritis and deafferentation pain. (See 'Complications' above.)

●Neuromodulation – Neuromodulation refers to the use of electrical stimulation to alter pain signaling (table 2). Examples include spinal cord stimulation and dorsal root ganglion stimulation, for which electrodes are placed percutaneously into the epidural space and the spinal neuroforamen, respectively. (See 'Neuromodulation' above and "Spinal cord stimulation: Placement and management".)

Peripheral nerve stimulators can also be placed for either acute or chronic pain. (See 'Peripheral nerve stimulation' above.)

●Intrathecal therapy – Intrathecal therapy involves the use of catheter and an implanted or external infusion pump to deliver analgesic medications and/or antispasmodics directly into the cerebral spinal fluid and the spinal cord. (See 'Intrathecal therapy' above.)