Pathophysiology

The amazing capacity of a peripheral nerve to regenerate after injury enables functional recovery in many cases. Unfortunately, this regenerative capability, when it goes awry, can produce a painful scar at the site of injury. Neuromas can affect any nerve: large, small, or microscopic. The key process that contributes to neuroma formation is the regrowth of injured axons into impenetrable scar. A traumatic neuroma is a dense, minimally vascular fibrous mass containing many small nerve fibers connected to a nerve.¹ The fibrous connective tissue that makes up the outer layer of the neuroma is continuous with the perineurium of the involved nerve.² The injured nerve fibers in a traumatic neuroma cause pain by multiple mechanisms. Spontaneous firing of nociceptors sends impulses centrally, leading to neuropathic pain.³ Additionally, nerve fibers in close proximity to each other may stimulate impulse transmission even in the absence of a synapse between them.⁴ Further stimulation may occur through the abnormal release of chemical pain mediators.⁵

Neuromas may form along nerves after injury, although it is a mystery exactly why they become painful in some cases and not in others. Typically, the traumatic event lacerates the nerve either partially or completely, although essentially any type of injury, such as compression, gunshot wound, or traction, can result in neuroma formation. When the nerve is completely severed (neurotmesis),⁶ the ends often retract apart. The proximal end sometimes forms a bulbous neuroma, whereas the distal end withers into scar (Fig. 170-1). Because the cut ends are physically separate, the probability of meaningful recovery of axons across the injured segment is vanishingly low.⁷ Sharp and blunt lacerating injuries often cause this type of neuroma.

FIGURE 170-1 Intraoperative photograph after exposure of a median neuroma at a mid-humeral level. This patient sustained a median nerve transection by glass from a broken window 5 months previously. The proximal nerve stump (P) has formed a bulbous neuroma, whereas the distal end (D) has thinned and scarred down to adjacent tissues. Note the significant retraction that has occurred, producing a substantial gap between the proximal and distal ends.

When the axons are severed but the epineurium remains intact (axonotmesis),⁶ this yields a neuroma-in-continuity. Compression, gunshot wound, and stretch injuries generally cause this type of neuroma. A fusiform neuroma may form along the injured segment (Fig. 170-2). Because the cut ends are together, meaningful recovery of axons across the injured segment often occurs (regenerating neuroma-in-continuity).⁸ The presence of scar, however, prevents recovery in some cases (nonconducting neuroma-in-continuity). These forms are distinguished most reliably by using intraoperative nerve action potential recordings. Recovering nerve action potentials are seen with a conducting neuroma-in-continuity, but not with a nonconducting neuroma-in-continuity (Fig. 170-3).

FIGURE 170-2 Intraoperative photograph after excision of a sural neuroma at a mid-calf level. This patient underwent a partial-thickness sural nerve biopsy 1 year previously. A fusiform neuroma has formed at the biopsy site, leaving the nerve in continuity.

FIGURE 170-3 Intraoperative photograph after external neurolysis of a sciatic nerve that sustained a blunt injury several months previously. The nerve has been subjected to an internal neurolysis as well, dividing it into its tibial and peroneal divisions. Hook electrodes are applied proximally and distally to the injured area, a stimulus (S) is applied, and intraoperative nerve action potential recordings (NAP) are obtained. The tibial division (top) shows a recovering nerve action potential, indicative of a conducting neuroma-in-continuity; whereas the peroneal division (bottom) shows a flat tracing, indicative of a nonconducting neuroma-in-continuity.

Clinical Presentation

Neuromas form after nerve trauma. Often, the patient is able to give a clear history of the traumatic event. In many cases, the nerve injury is obvious. Sometimes, neuromas form unexpectedly after surgery following an unrecognized nerve injury. In other cases, neuromas form following a prolonged period of mild, repetitive injury. At times, a large, named nerve is injured, and in other cases, a small, unnamed sensory nerve forms the neuroma. When a nerve is acutely injured, it may be sensitive to touch or pressure immediately after injury. Sometimes this sensitivity persists until a neuroma forms. Sometimes nerves are not particularly painful in the early period after injury but become sensitive later on once the neuroma forms. It is unclear why some nerve injuries are painful immediately and others become so in a delayed fashion.

Traumatic neuromas are firm, slow-growing, and sometimes palpable nodules that can be associated with pain and paresthesias in the affected area. The hallmark finding for a painful neuroma is an exquisitely sensitive, focal area along the course of a previously injured nerve. Pain is evoked by palpation of the region and may remain local or radiate along the course of the peripheral nerve sensory distribution (Tinel’s sign).⁴ Patients can also have tenderness and hypersensitivity to normal tactile stimuli in the surrounding regions.² When the injured nerve is nonfunctional, there is often loss of sensation in the distribution of that nerve.

Diagnosis

The diagnosis of a neuroma can be made clinically: pain in the region of a scar, altered sensation in the distribution of the affected nerve, and Tinel’s sign. Confirmatory testing may include injection of local anesthetic into the vicinity of the neuroma⁹ or more proximally along the course of the affected nerve.¹⁰ The presence of temporary pain relief helps make the diagnosis of a painful neuroma and additionally may help to identify the exact nerve involved. This may be helpful if multiple candidate nerves are in the vicinity, such as in the inguinal region. Some practitioners use control injections of saline or local anesthetics of differing durations, one long acting and one short acting, in an effort to increase reliability of this diagnostic modality. Such a strategy may help reduce unwanted placebo effects, which can complicate the treatment of any pain disorder.

Imaging may be used to identify larger neuromas. Magnetic resonance imaging and magnetic resonance neurography may delineate the neuroma clearly in some cases.¹¹ Ultrasonography has been additionally used routinely to image Morton’s neuromas, affecting the plantar digital nerves that form near the metatarsal heads after repetitive compression trauma.¹²

Perhaps the most reliable way to identify a neuroma is with surgical exploration in the awake patient. Following external neurolysis of the neuroma, when palpation of the neuroma reproduces the patient’s exact pain, little diagnostic uncertainty remains. This strategy is essentially identical, in theory, to the conscious pain mapping procedures used by gynecologists during laparoscopic procedures to identify pelvic pain generators.¹³

Treatment

When a painful neuroma is diagnosed, a comprehensive, pain management–oriented approach may be helpful. Initial efforts may involve over-the-counter pain medications and protecting the painful area from additional trauma. Anticonvulsant¹⁴ and antidepressant¹⁵ medications may provide relief for neuropathic pain. Opiates¹⁶ may also reduce pain levels. Complementary and alternative therapies such as acupuncture may be useful.¹⁷

When these noninvasive efforts are insufficient, a more aggressive strategy may be required. Steroid injections, sometimes coupled with a local anesthetic, may provide temporary and, in some cases, durable pain relief.¹⁸ Ablative techniques such as radiofrequency ablation, pulsed radiofrequency ablation, or chemical neurectomy¹⁹ may destroy the associated nerve or neuroma, providing the necessary pain relief. There is a paucity of high-quality clinical data supporting the use of these techniques, however.

Open surgery is another option in the treatment of painful neuromas. A major problem in neuroma excision is the recurrence of the neuroma, and prevention of growth of a secondary neuroma is a key part of surgical treatment. In the past, treatment of neuromas involved neuroma excision followed by capping the nerve with many substances, including silicone and surplus epineurium, to prevent new neuroma formation.²⁰ Additionally, chemical treatment of the cut proximal end of the nerve has been used.²¹ One study reported that oblique transection of peripheral nerves, as opposed to perpendicular transection, greatly reduces the rate of classic neuroma development.²² Additionally, this method of oblique transection was thought to significantly reduce neuropathic pain compared with that following the traditional form of nerve transection.

A different surgical strategy emphasizes placement of the cut end of nerve into an appropriate environment and does not attempt to physically restrain axonal outgrowth.²³ Using a primate model of a neuroma, transection of the radial sensory nerve at the wrist, followed by turning the sensory nerves proximally and implanting them into a forearm muscle, effectively prevented classic neuroma formation. Specifically, the sensory nerve showed no signs of regeneration when implanted into the muscle.²⁴ Meyer and colleagues²⁵ produced superficial radial nerve neuromas in a group of baboons and found that neuromas produce spontaneous activity of pain fibers and are sensitive to mechanical stimulation. Thus, muscle reimplantation may also reduce pain caused by mechanohypersensitivity by decreasing the mechanical stimulation encountered by the neuroma.²⁴ In a study by Burchiel and colleagues²⁶ of 18 patients with distal sensory neuromas, reimplantation of nerve endings showed a success rate of 44% and an average drop in visual analog scale–registered pain of 32%. Dellon and Mackinnon²⁷ found that 80% of patients had excellent pain relief after neuroma resection and reimplantation into muscle. They suggested that the nerve must be directed into muscle without tension in a distal-to-proximal direction to accommodate the minimal amount of nerve regeneration that will inevitably occur and should be implanted in muscles with minimal excursion to keep the implanted nerve in place. Additionally, if the nerve is implanted near the deep surface of the muscle, regeneration into the overlying skin is prevented, thus reducing mechanical stimulation of the nerve.²⁸

Using these general surgical principles, painful neuromas in a variety of locations may be treated. When a painful neuroma is suspected based on history and physical examination, an attempt is made to identify the nerve based on pain distribution and sensory loss. Local anesthetics are used to confirm the diagnosis. After noninvasive treatment measures fail and percutaneous ablative techniques are deemed ineffective or inappropriate, surgical neurectomy is considered.

For superficial neuromas along named peripheral nerves, an attempt is made in the mildly sedated patient to subject the nerve to an external neurolysis and definitively identify the nerve. Palpation of the suspected neuroma should reproduce the patient’s pain (Fig. 170-4). Once located, the nerve is sectioned proximal to the neuroma, and the neuroma is removed. When the nerve arises from muscle proximally, such as the plantar digital nerves, the lateral femoral cutaneous nerve, or the abdominal nerves such as the iliohypogastric and ilioinguinal, sectioning the nerve under tension allows it to retract into the muscle. Once in muscle, the likelihood of neuroma recurrence is reduced. If the nerve does not arise from nearby muscle, the nerve may be transposed to a nearby muscle, implanted through a small incision in the muscle belly, and sutured into place (Fig. 170-5).

FIGURE 170-4 Intraoperative photographs during surgical excision of a painful sensory neuroma that formed along the iliohypogastric nerve after a laparoscopic procedure. With the patient under mild sedation, a conscious pain mapping procedure is performed. Local anesthetic is infiltrated into the skin only. Palpation of the deeper tissues reveals the painful area, subjacent to the fascia, which is marked with an X (top). Once the fascia is opened, the nerve and a fusiform neuroma become apparent (bottom). Pinching the neuroma with forceps reproduces the patient’s pain exactly. With the nerve under traction, the nerve is transected proximal to the neuroma, and the proximal end of the nerve is allowed to retract into the muscle belly. This reduces the likelihood of neuroma recurrence. The distal end is then cut, enabling excision of the entire neuroma. The distal side is cut second so that the patient only experiences a single nerve transection sensation.

FIGURE 170-5 Intraoperative photographs of a patient who sustained an iatrogenic injury to the superficial radial sensory nerve during an orthopedic surgical procedure a few months previously. The upper image shows a typical bulbous sensory neuroma (N) at the site of nerve transection. The lower image shows the result after neuroma excision, with implantation (I) of the distal end of the nerve into the brachioradialis muscle. The sutures anchor the nerve into the muscle to prevent pullout with arm movement during the postoperative period.

For superficial neuromas along unnamed, cutaneous sensory nerves, a conscious pain mapping procedure is used. First, the painful area is marked in the preoperative area with the patient fully awake. Once in the operating room, an incision is made over the painful area using local anesthetic in the skin. Progressively deeper dissection through nonanesthetized tissues enables identification of the discrete painful area in the awake patient. The tissue is excised with the patient temporarily rendered unconscious by the anesthesiologist. Repeat probing of the surrounding tissues is performed with the patient awake to find and remove any additional painful areas, which presumably contain the responsible mechanosensitive tissue.

The practicing neurosurgeon may encounter cases in which neuroma excision surgery is inappropriate. For example, patients who have already undergone one or more failed neuroma excision surgeries, in our experience, do not experience pain relief with additional neurectomy surgery. We can only speculate as to the reason at this point, but centralization of the pain generators and psychological factors may play a role. Postamputation neuromas of large, mixed nerves such as the sciatic nerve may be especially problematic for the surgeon. Wound healing in these regions may be fraught with difficulties. In most cases, unless there is a clear-cut structural abnormality in a stump, such as a sharp end of bone cutting into the nerve, local excision surgery should probably be avoided.²⁹

When surgical excision of neuromas is thought to be inappropriate and patients have failed less invasive measures, interventional pain management techniques may be used. Specifically, neurostimulation can be quite helpful, depending on the distribution of pain.³⁰ Neuroma pain in the extremities can generally be treated with spinal cord stimulation. Spinal nerve root stimulation, which targets pain-relieving stimulation paresthesias into the distribution of single or multiple nerve roots, may provide relief to patients with pain in the hands, feet, inguinal regions, pelvic regions, and intercostal distributions.³¹ These areas are often unreachable with spinal cord stimulation. Small regions of neuroma pain, inaccessible to spinal nerve root or spinal cord stimulation, may be targeted effectively with subcutaneous peripheral nerve stimulation³² in which the electrodes are placed under the skin at the site of pain (Fig. 170-6).

FIGURE 170-6 Intraoperative photograph of a patient who developed a sensory neuroma near her incision following a hip replacement. Her painful area was marked (hatched area) using a conscious pain mapping procedure intraoperatively. Two subcutaneous stimulator electrodes were placed within the painful region. Intraoperative testing revealed good overlap of the stimulation paresthesias with her painful area. During her 1-week external trial, she experienced significant pain relief, and she later underwent permanent placement of the stimulator system.

Future Directions

Currently, the surgical treatment of painful neuromas is crude, and the field has advanced little in recent years regarding definitive treatments. The most notable advancements have been in neurostimulation, with novel applications of electrical stimulation targeting pain relief to specific painful areas and limiting unwanted paresthesias in adjacent, nonpainful areas. Future studies should establish whether these less invasive techniques, as well as the percutaneous ablative techniques such as radiofrequency ablation, are effective. Ultimately, prevention of neuroma formation by inhibiting axonal growth into the nerve scar would be ideal. Perhaps nerve growth inhibitors could be injected into injured nerves before neuroma formation, or perhaps a method of pharmacologically silencing mechanosensitive nerves subsequent to neuroma formation would be a comparably effective strategy.