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Unremitting pain after uncomplicated hand surgery can frustrate both surgeon and patient. For example, the incidence of surgical site pain after carpal tunnel release has been estimated to be as high as 59% by some.1–3 This pain may be incisional, periincisional (so-called “pillar” pain), or in the distribution of the cutaneous supply of the median nerve.4,5 Although the reasons behind postoperative chronic pain are multifactorial, one cause may be entrapment of cutaneous nerve in the surgical scar. As we will describe, cutaneous nerve entrapment can result in deep, diffuse pillar pain.
On presentation, the symptoms of cutaneous nerve injury may be nonfocal and may present a diagnostic dilemma. Some patients present with the classic Tinel sign or scar dysesthesia; however, on occasion the patient complains of vague pain that is not isolated to a single peripheral nerve distribution. These seemingly nonanatomic symptoms are secondary to a host of pathologic changes that occur in response to nerve injury and that are becoming clear with ongoing pain research.
Nociceptors are a special subset of sensory neurons that transduce the sensation of pain. At baseline, these nociceptors only reach action potentials and fire when subjected to high levels of stimuli (usually close to the amount of stimulation associated with tissue injury).6 Several authors have demonstrated that trauma to these nerves can alter their phenotype. After injury, these nerves demonstrate up-regulation of sodium channels,7,8 adrenergic receptors,9–12 and nicotinic cholinergic receptors.13 These up-regulated proteins generate depolarizing currents that can confer a pacemaker-like effect to the nociceptors, which will then repetitively depolarize and cause the transmission of an action potential in the absence of external stimuli.
The unrelenting barrage of nerve impulses from injured peripheral nociceptors increases the excitability of adjacent uninjured pain-transmitting neurons in the spinal cord. This is called central sensitization.6,14 Multiple levels of the spinal cord can be activated in central sensitization because incoming peripheral sensory fibers can cross several spinal segments before finally synapsing with their second-order neurons in the dorsal gray matter of the ipsilateral spinal cord.15,16 For example, axonal fibers of the ulnar nerve enter the cord at C8 and T1. Yet, the ulnar nerve has been shown to have synapses with second-order neurons in both higher and lower spinal segments, including C6 and C7—areas that are stimulated by fibers of both the median and radial nerves. An injury to a terminal cutaneous branch of the ulnar nerve can result in central sensitization that spans multiple spinal segments and can therefore cause pain to be perceived in both the median and radial nerve distributions.
The pain pathways are complex, and at each level physiologic changes can occur with chronic pain. The nociceptors primarily synapse in the dorsal horn of the spinal cord, and then the pain signal ascends via the spinothalamic tract diverging at the thalamus. Separate neuroanatomic pathways regulate the sensory–intensity and affective–unpleasantness components of pain. The ventrolateral posterior thalamic nucleus and somatosensory cortex provide information on where the pain is, how much area it covers, and what it feels like. Other areas including the ventromedial posterior thalamic nucleus and its cortical connections create the affective/motivational aspects of pain; for example, the “aversiveness” of the sensation, the drive to escape, and fear of the pain.17–19 The anatomy is such that the more intense the pain becomes, the more it will be perceived in a poorly localized way. This is due to the recruitment of second-order neurons that under normal circumstances represent other anatomic areas in neighboring spinal segments. This physiology may explain the “spreading” of pain seen in patients with complex regional pain syndrome in which neuralgic pain crosses boundaries defined by peripheral nerve distributions. These physiologic changes also ensure that many patients with cutaneous nerve injuries and “scar neuromas” complain not of superficial shooting or electrical pain at the scar but rather deep, diffuse, poorly localized, aching or throbbing pain that the patient may only occasionally localize to the scar. Patients therefore attribute their sense of deep, persistent, poorly localized pain to ongoing pathology in the area that was the target of the original surgery; in actuality, their pain is pathologic activation of both peripheral and central pain pathways.
The diagnosis of this problem is made through an appreciation of the functional neuroanatomy and a high level of vigilance. If the surgeon suspects a cutaneous neuroma, intradermal injection of the scar with lidocaine will be diagnostic. After injection, the patient will get instant relief, generally encompassing the whole area of their pain including the areas that seem to be in another nerve’s distribution. Treatment, however, is not as clear, as both surgical and nonsurgical interventions have been described with varying degrees of success.20,21
Most surgical approaches share in common a resection of the cutaneous nerve, suggesting that cutaneous scar may represent a uniquely bad place for an injured nerve.22,23 The skin itself is richly innervated with adrenergic and cholinergic efferents from the sympathetic and parasympathetic nervous systems, and in this environment, increased expression of adrenergic receptors and nicotinic cholinergic receptors on injured peripheral nerve endings results in increased pain and firing rates of the nociceptive neurons.12,13,24,25 As yet, no surgical standard has emerged.
Nonsurgical approaches to the cutaneous neuroma have included injection of neurolytic solutions in various formulations,26,27 spinal cord stimulation,28,29 peripheral nerve stimulation,30,31 local anesthetics, and botulinum toxin.32 Botulinum toxin inhibits acetylcholine release from cholinergic nerves in the skin in a long-standing, but ultimately fully reversible, manner.33 It may work by decreasing stimulation of nicotinic cholinergic receptors on injured nociceptors or through other mechanisms such as inhibition of calcitonin gene-related peptide release from nociceptors.34,35 If proven effective, botulinum toxin may have advantages over previous neurolytic techniques because of an improved safety profile. Botulinum toxin has less risk of worsening symptoms in a permanent way and there is a decreased incidence of skin breakdown when compared to the injection of more caustic substances such as alcohol.
Future research will continue to focus on understanding the transformation of some cutaneous nerves into sources of chronic pain. The fact that most traumas including surgery do not result in chronic pain indicates that the majority of cutaneous nerve injuries do not transform into chronic pain centers. Some evidence indicates that the central nervous system’s responses to injury may be as critical as the mode of injury in ultimately determining clinical outcome with respect to pain.36–38 Within this context, the next horizon is to assess if we can therapeutically target the central nervous system response to injury to reduce the incidence of posttraumatic chronic pain. Pilot studies in humans indicate that ketamine,39 intrathecal clonidine,40 and epidural local anesthetic41 each when given at the time of injury may reduce the proportion of patients who go on to have chronic postsurgical pain. Animal studies further suggest that medications such as the antibiotic minocycline, which also has glial cell inhibitory properties, may prevent the development of chronic nerve pain when given at the time of, but not after, injury.38 Further understanding of the perioperative central nervous system response to nerve trauma and head-to-head studies comparing techniques to prevent and treat scar neuromas hold promise to improve surgical outcomes and reduce postoperative morbidity.
Supported by a VA Career Development Award (C.C.).