Pain and Peripheral Nerve Injury

Neuropathic pain and neuralgia are two common terms that many clinicians use interchangeably. Their definitions remain broad and include pain related to an injury or abnormality of a peripheral nerve (i.e., neuropathic pain) and pain in the cutaneous distribution of a peripheral nerve (i.e., neuralgia).¹ There are additional categories of peripheral nerve-related pain, summarized in Table 246-1. Although some categories have distinct etiologies, symptoms, and treatments, significant overlap remains, as does continued disagreement with the classification system currently being used.¹

The etiology of peripheral neuropathic pain is likely multifactorial.² In general, the following processes likely contribute:

The exact relationship between sympathetic outflow and pain remains uncertain, however, transient improvement in some patients after sympathectomy strongly supports this connection.⁴ Pathophysiologic changes in the spinal cord and periaqueductal gray matter can centralize pain so that pain remains despite nerve blocks and other peripheral treatments being applied.

Diagnosis and classification of pain is predominantly based on the history and physical examination. Response to trial medications, autonomic changes, and temporary improvement with nerve blocks may help refine the cause. When taking a history, the location, quality (e.g., burning, paresthetic, crushing), and any exacerbating and relieving maneuvers, should be discussed with the patient. With peripheral nerve entrapment, pain is often referred adjacent to, and along, the distribution of the compressed nerve. For example, the description of aching discomfort in the wrist and forearm, along with nocturnal symptoms, including paresthesias in the median nerve distribution, are characteristic of carpal tunnel syndrome. Pain and tenderness may also be present at the entrapment site (e.g., near the fibular head with peroneal nerve entrapment at the knee). When peripheral nerves without cutaneous sensory afferents are injured, numbness and paresthesias do not occur; however, a deep aching pain may be present not only at the point of entrapment but also within any joints the entrapped nerve carries proprioceptive sensation from (e.g., dorsal wrist pain when the posterior interosseous nerve is compressed in the proximal forearm; shoulder pain with the early stages of suprascapular entrapment neuropathy). When significant damage to a motor-sensory nerve occurs, concomitant sensory abnormalities, including paresthesias, hypoesthesias, and hyperesthesias, are characteristically present in the nerve’s sensory territory.⁵ The clinician must keep in mind that sensory loss may be unreported because of more severe, overlying pain.

Autonomic disturbance, in part, may also cause significant pain in patients with peripheral nerve injuries and is a hallmark of both type I (formerly known as reflex sympathetic dystrophy) and type II (formerly known as causalgia) complex regional pain syndrome (CRPS) (Fig. 246-1).⁶ CRPS type I usually occurs after a minor injury to the extremity (e.g., sprained ankle), whereas CRPS type II occurs after significant damage to a major mixed nerve (e.g., gunshot wound). Severe burning pain, careful attempts to protect the involved extremity from movement or manipulation, and evidence of autonomic overactivity (or underactivity) are features of both CRPS types I and II. Trophic changes such as dry skin, nail loss or nail changes, and vascular changes such as skin flushing and discoloration and temperature fluctuations are hallmarks of this disarrayed autonomic activity. Furthermore, denervation hypersensitivity to circulating or local catecholamines may also exacerbate nerve pain and likely contributes to worsen pain during periods of environmental and emotional stress.

FIGURE 246-1 A, This patient has complex regional pain syndrome (CRPS) type I affecting her right hand. Atrophy and pallor compared with her normal left hand is evident. Also note her avoidance of jewelry on her right hand and forearm. She sprained her wrist rollerblading and has no evidence of nerve injury on electrodiagnostic testing. Transient improvement occurred following a cervical sympathetic block. B, A patient with severe burning pain consistent with CRPS type II affecting his right leg following a buttock-level gunshot wound to the sciatic nerve. Swelling, alopecia, erythema, and atrophy of the patient’s right distal extremity are present. He cannot wear a normal shoe on his right foot and requires the use of a soft sock and specialized orthopedic boot for ambulation.

Another type of pain that may occur with nerve injury is avulsion pain (this falls under the broader category of deafferentation pain). This is usually a result of nerve root avulsion from the spinal cord. Avulsion pain usually manifests as a constant burning or crushing pain that is poorly responsive to physical therapy, medication, and nerve blocks. Regenerating nerves may also produce pain, often described as tingling, electric shocks, and dysesthesias along the course of the nerve; this type of pain is usually considered a normal sign of the regeneration process. Patients with neuromas usually describe localized pain, with a trigger point overlying an often palpable, exquisitely tender subcutaneous neuroma. A diagnostic nerve block near the neuroma can usually confirm this diagnosis.

Management of neuropathic pain remains challenging, with many patients having only partial or minimal relief with treatment. Those with complicated, chronic, or refractory nerve pain should be referred to a pain center where a comprehensive evaluation and treatment plan can be instituted based on a multidisciplinary consensus. In general, treatment options may be divided into the following categories: physical therapy, pharmacotherapy, local and proximal nerve blocks (e.g., sympathectomy), psychological counseling, local surgical intervention (e.g., neuroma removal), and peripheral and central nervous system stimulation. A stepwise trial of progressively more invasive treatments should be recommended based on the clinical situation. Stimulation has increased in popularity in recent years. It has been proved effective for postherpetic neuralgia and CRPS and less effective, but commonly used, for peripheral neuropathy, avulsion pain, and failed back syndrome.⁷ Peripheral nerve stimulation has for the most part been replaced by spinal cord stimulation for pain in the extremities. This is because of the ease of spinal stimulator trials and permanent implantation; however, occipital and frontalis peripheral nerve stimulation remain excellent options for neuralgia affecting these nerves.⁸ An important concept for peripheral nerve stimulation is that the pain should be solely localized to the distribution of the affected nerve for the stimulation to be effective.⁸ Central nervous system ablative surgery also maintains a role in contemporary pain management.⁷ Indications include dorsal root entry zone (DREZ) ablation for avulsion pain and radiofrequency ablation of the descending sensory trigeminal tract for treatment of anesthesia dolorosa affecting the trigeminal nerve and for certain forms of cancer pain.

Complications and Their Avoidance in Peripheral Nerve Surgery

In performing peripheral nerve surgery, as with any area of surgery, knowledge of the anatomy is of the utmost importance. The surgeon must not only understand the nerve anatomy but also be able to correlate neural structures with their target muscles and sensory distribution. Knowledge of the vascular and bony anatomy will also be essential to planning the surgery. In much of nerve surgery, the normal anatomy is distorted, whether from trauma, tumor, or other pathology, and the surgeon must have a clear anatomic picture of the normal anatomy before proceeding. A properly planned incision and exposure will allow for the correct identification of the vital structures as well as room in which to perform the needed tasks. Failure to be thoroughly informed about the relevant anatomy is probably the most common cause of iatrogenic nerve injury.

Avoiding complications during peripheral nerve surgery often requires an understanding of principles and techniques that are distinct from those used for the brain and spine.⁹ Furthermore, because most neurosurgery training programs do not perform a high volume of peripheral nerve surgery, many residency graduates do not possess the experience and understanding needed to minimize complications during peripheral nerve surgery, even though many will subsequently perform these procedures in their practice.¹⁰ In this section, we review how fundamental errors, such as misdiagnosis, misidentification, poor operative timing, and other operative errors, may predispose to complications. The complications for several types of peripheral nerve surgery (e.g., brachial plexus repair, carpal tunnel release) are summarized in Table 246-2. A more in-depth review can be found elsewhere.^11,12

TABLE 246-2 Select Peripheral Nerve Surgery Complications

More than for most neurosurgical diseases, lesion localization in the peripheral nervous system relies on an accurate history and physical examination. In fact, many peripheral nerve operations are performed without radiographic confirmation of the diagnosis. When investigating most peripheral nerve entrapments or injuries, most imaging modalities, including plain films, computed tomography (CT) scans, magnetic resonance imaging (MRI), and ultrasound, either have poor sensitivity and specificity, are not yet fully evaluated as diagnostic tools in the peripheral nervous system, do not provide information that changes management, or have a poor predictive value for clinical outcomes. Nevertheless, imaging plays an important role in peripheral nerve surgery. CT myelography or MRI are necessary when investigating root avulsion, and CT or MRI is necessary for the exclusion of mass lesions, including nerve sheath tumors, ganglion cysts, and lipomas. The clinician should have a low threshold for ordering an imaging study when a structural lesion is suspected. Without the correct preoperative diagnosis, opportunities to repair nerve injuries may be missed, inappropriate and potentially dangerous surgeries may be performed, and a patient may be offered more invasive therapy when a simpler option is available (Fig. 246-2).

FIGURE 246-2 An example of a misdiagnosis contributing to a poor outcome. This patient fell on an outstretched left arm and developed numbness in his left distal forearm and medial palm, excluding the tip of the fifth digit. Transient back and shoulder pain and stiffness were present for about 1 to 2 weeks. He underwent two ulnar nerve decompressions without improvement based on a nerve conduction study revealing mild slowing in the ulnar nerve across the elbow. On closer examination, a partial left Horner’s syndrome (A) led to further imaging (computed tomography myelogram) that revealed marked left T1-2 foraminal stenosis compressing the T1 nerve (B), perhaps related to his previous fall. Foraminotomy lead to an immediate, albeit partial, improvement in his numbness.

Once the etiology and location of nerve injury has been established, a decision to operate must be made. Many nonpenetrating, nerve injuries represent focal conduction blocks (neurapraxia) that usually recover without the need for surgical intervention. Therefore, in general, injuries without documented nerve transection, multiple nerve rootlet avulsions, or a persisting compressive force (e.g., hematoma) should be followed expectantly for about 3 months to rule out neurapraxic injury. Earlier operation in these patients should be avoided because this may lead to iatrogenic injury or a worsened outcome.

For more severe nerve injuries in continuity (axonotmesis), which by definition cause wallerian degeneration and possible axonal regeneration, acceptable outcomes may also occur without surgical intervention. In these instances, the clinician should closely monitor, both with serial neuromuscular examinations and electromyography, the patient’s progress. If no recovery occurs by about 3 months, prompt operative exposure and intraoperative nerve recordings across the injury are indicated to rule out the need for graft repair of a nonconducting neuroma-in-continuity.¹³ Not doing so may lead to a missed opportunity for repair and poor outcome.

When a neuroma-in-continuity is encountered during surgery, it is not possible by palpation and visual inspection to know whether the injured segment contains viable axons, which have not, as of yet, reached their target muscles. In general, neuromas-in-continuity conducting evoked potentials should not be resected because their recovery following external neurolysis alone is better than that seen with grafting or primary repair.¹⁴ Use of nerve stimulation alone with selective electromyographic recordings from muscle is not recommended because sampling from a few areas of muscle can miss axons innervating other areas not being recorded. Also, because some axons that have regenerated through the damaged segment may not have reached a muscle yet, these would be missed. Although a positive finding, it only takes a hundred or so regenerating nerve fibers reaching muscle to have an evoked muscle action potential, and yet thousands are necessary to have good recovery of function. When resecting nonconducting neuromas-in-continuity, one should make certain to trim back the nerve ends until healthy, pouting fascicles are apparent and good bleeding points are encountered. One should not accept leaving behind residual neuroma in hopes of achieving end-to-end repair or allowing shorter graft length; doing so will result in poor regeneration.

It is understood that clean, sharp nerve transections should be repaired urgently (i.e., in less than 72 hours). However, one should avoid performing immediate repairs of blunt transections.¹⁵ Blunt transections include chainsaw, gunshot (although most gunshots do not cause transections), degloving wounds with substantial tissue loss, and other high-speed, penetrating wounds, both clean and contaminated. In addition to the transection, they also have a significant blunt or stretch component. These injuries should be repaired about 2 to 3 weeks after injury so that any contusive or stretch damage to the nerve ends, which commonly occurs with blunt transections, has time to demarcate and visually manifest. Using this delayed approach, one avoids inadvertently coapting damaged, and eventually neuromatous, nerve ends (Fig. 246-3). This approach also avoids repairing nerves in a contaminated wound. Bluntly transected nerves that are found during an emergent exploration for concurrent vascular or orthopedic injuries should be tacked down to adjacent fascial planes, which helps minimize nerve end retraction. The wound is then reexplored about 2 to 3 weeks later, and the nerves may then be repaired without fear of having coapted nonviable nerve.

FIGURE 246-3 An example of poor timing for nerve repair contributing to a suboptimal outcome. A 20-year-old patient underwent a direct suture repair the same day his peroneal nerve was bluntly transected by a propeller blade. A, There was no evidence of recovery by 1 year, at which time the previous repair was reexplored revealing a large neuroma-in-continuity directly centered on the suture line (asterisk) and a distally scarred, atrophic nerve (between arrowheads). B, The abnormal nerve segment was removed, leaving a 5-cm gap between the proximal (arrow on left) and distal stumps (arrows on right). C, Four sural nerve grafts were placed (arrows). This blunt transection should have been explored 2 to 4 weeks after injury so that any abnormal nerve segments would have had time to become evident (and resected) before repair.

Iatrogenic Peripheral Nerve Injuries

Nerve injury may occur during almost any invasive procedure.¹⁶ Nerves may be directly damaged in the operative field or compressed secondary to poor patient positioning on the operating room table, especially for longer procedures under general anesthesia.

Iatrogenic Injury during Nonperipheral Nerve Surgery

Considering peripheral nerves course throughout the body, they may be injured during almost any open or percutaneous procedure, including bedside venous and arterial punctures. Some of the more common types of iatrogenic nerve injuries are summarized in Table 246-3. During surgery, peripheral nerves may be damaged from excessive retraction (usually by a sharp, self-retaining retractor), coagulation, transection, postoperative swelling, or accidental stapling or ligature of a nerve (Figs. 246-4 and 246-5).

TABLE 246-3 Common Iatrogenic Nerve Injuries

NERVE	MECHANISM	COMMENTS
Spinal accessory nerve	Injured during cervical lymph node biopsy	May be misdiagnosed considering the levator scapulae also shrugs the shoulder; minimized with use of intraoperative stimulation before biopsy
Ilioinguinal nerve	Injured during inguinal hernia repair	May occur with open or laparoscopic hernia repairs; genitofemoral and iliohypogastric nerves may also be affected
Sciatic nerve	Injured during hip replacement	Secondary to retraction, transection, suture misplacement, or postoperative swelling
Peroneal nerve	Injured during knee replacement and gynecological procedures	Secondary to retraction, transection, suture misplacement, or postoperative swelling or improper padding while in stirrups
Ulnar nerve	Compression or stretch injury related to operative positioning	May be from direct nerve compression in retrocondylar groove or from prolonged flexion of the elbow
Brachial plexus	Stretch injury related to operative positioning	May occur after prone spine surgery with shoulders pulled down for fluoroscopy exposure, or from excessive abduction and external rotation in the supine position
Lateral femoral cutaneous nerve	Compressive injury from prolonged spine procedures in the prone position	Common after long spine surgery procedure in the prone position, but resolves spontaneously in most patients. May be injured while taking of iliac crest graft

FIGURE 246-4 This patient underwent a cervical lymph node biopsy and suffered an iatrogenic spinal accessory nerve palsy. A, Operative positioning and incision for the subsequent reexploration; previous biopsy incision (between arrowheads) was incorporated in the new incision. B, A transected and retracted spinal accessory nerve was identified (proximal stump between arrowheads on left; distal between arrowheads on right). The greater auricular nerve is in the white loop. C, Two nerve grafts (arrowheads) from the greater auricular nerve were used to repair the damaged nerve.

FIGURE 246-5 Iatrogenic peroneal nerve injury secondary to varicose vein stripping. A, After vein stripping, sagittal knee magnetic resonance imaging reveals extensive varicosities (arrow) within the epineurium of the common peroneal nerve. B, At reoperation, an injury to the peroneal nerve was identified (overlying the blue rubber square) as well as two unusually large lateral sural cutaneous branches. C, Cross section of a lateral sural cutaneous nerve revealing both nerve fascicles and multiple varicosities within the epineurium. D, A short segment of the peroneal nerve was removed and grafted with sural nerve. The uninjured tibial nerve lies above and adjacent to the grafted peroneal nerve. Varicosities were also noted within the common peroneal nerve when it was repaired. Presumably, a vein was “stripped” as it entered the common peroneal nerve through the lateral sural cutaneous nerve.

Conclusion

Many of the complications that occur during peripheral nerve surgery are preventable. Therefore, surgeon education is paramount for improving patient outcomes. There should be more discussion of peripheral nerve complication avoidance in training programs, at national meetings, and in the results section of published clinical studies. Early and accurate diagnosis of nerve pain, complications, and iatrogenic injury allows for optimal management and an acceptable recovery in many patients. A significant delay in diagnosis may lead to the development of chronic pain syndromes and permanent nerve injury.