Surgically induced neuropathic pain: understanding the perioperative process

Abstract

Nerve damage takes place during surgery. As a consequence, significant numbers (10%-40%) of patients experience chronic neuropathic pain termed surgically induced neuropathic pain (SNPP). The initiating surgery and nerve damage set off a cascade of events that includes both pain and an inflammatory response, resulting in "peripheral and central sensitization," with the latter resulting from repeated barrages of neural activity from nociceptors. In affected patients, these initial events produce chemical, structural, and functional changes in the peripheral and central nervous systems (CNS). The maladaptive changes in damaged nerves lead to peripheral manifestations of the neuropathic state-allodynia, sensory loss, shooting pains, etc, that can manifest long after the effects of the surgical injury have resolved. The CNS manifestations that occur are termed "centralization of pain" and affect sensory, emotional, and other (eg, cognitive) systems as well as contributing to some of the manifestations of the chronic pain syndrome (eg, depression). Currently there are no objective measures of nociception and pain in the perioperative period. As such, intermittent or continuous pain may take place during and after surgery. New technologies including direct measures of specific brain function of nociception and new insights into preoperative evaluation of patients including genetic predisposition, appear to provide initial opportunities for decreasing the burden of SNPP, until treatments with high efficacy and low adverse effects that either prevent or treat pain are discovered.

Figure 1. Overall Concepts

1. Pre-surgical condition. Patients may have premorbid conditions including ongoing acute or chronic pain, psychobiological or genetic conditions that may predispose to chronic pain following nerve damage.

2. Surgery and Perioperative Events. Surgery may set of a cascade of events including pain. Pain is not always prevented during surgery and complete pain control is difficult to obtain throughout the perioperative process.

3. Temporal Processes. A cascade of events unfold – after nerve damage aside from afferent bursts of activity that travel to the CNS the nerve begins to unfold that includes central sensitization, a process that may be concurrent with nerve damage and in the perioperative period or as the neuropathic pain state, and centralization of pain where alterations in the CNS take place (see Text). . Most of these brain changes are difficult to reverse by medications. One surgical example relates to removing pain sources in a chronic nociceptive pain syndrome, hip osteoarthritis, where brain changes in cortical volume can be reversed by hip arthroplasty (see (Rodriguez-Raecke et al., 2009; Gwilym et al., 2010)

4. Neurobiological Processes. Following surgical trauma a number of events occur secondary to nerve damage as noted. In the peripheral nerve and spinal cord a number of processes occur including ectopic generation pain potentials, facilitation and disinhibition of pain transmission, loss of synaptic connectivity and formation of new synaptic circuits (Costigan et al., 2009). More centrally (i.e., CNS) facilitation or disinhibition of modulatory circuits is observed in the brainstem (Gardell et al., 2003) or in cortical regions (Schwenkreis et al., 2010; Lenz et al., 2011) (see Text).

Figure 2. Nociception and Pain in the Perioperative Period

Damage to the nerve and nociceptive afferent barrage in the pre-, intra- and postoperative period may contribute to central sensitization and result in changes in the peripheral and central nervous system. Ideally, minimal or no pain should be experienced throughout the perioperative period. However, pain may either be a significant problem during anesthesia (not measured) and/or postoperatively. Complicating any of these patterns is any premorbid pain process. Any barrage of pain may contribute to central sensitization and potentially the chronification from acute pain to chronic pain (See Text).

Figure 3. Intermittent Nociceptor Activation (fiber burst activity) across the perioperative state

Shown in this figure are types of pain that may be produced during the perioperative period. Type 1, probably the most severe, results from actual nerve damage and inflammation resulting from surgical trauma. Type 2, is a result of analgesic wear-off during surgery. Type 3 is similar to Type 2, but is present in the post-operative period. The latter may be a result of ongoing nociceptive pain during recovery or the result of neuropathic pain. Different activation patterns may be observed across the peri-operative perioid (see B below).

Figure 4. Development of Objective Markers for Nociception (and Pain) and Awareness in the Operating Room

Measures of brain function that can accurately define intraoperative nociceptive activation in brain regions would allow for improved measures of analgesia during surgery. Such changes may have implications for diminishing central sensitization in the postoperative period and potentially limit changes that may contribute to long-term neuropathic pain.