When Does Acute Pain Become Chronic?

When Does Acute Pain Become Chronic?

C Voscopoulos1, M Lema1

1University at Buffalo, Department of Anaesthesiology, Buffalo, NY

Introduction

Pain-related problems account for up to 80 percent of visits to physicians.  The epidemiologic significance of chronic pain after surgery is enormous [1]. The prevalence of chronic pain can range from 10.1% to 55.2% of the populations studied [2]. Current theories proposethat a prolonged experience of acute pain in which long standing fundamental changes are seen within and external to the central nervous system, creates chronic pain with a histologic and pathologic basis 3]. Furthermore, chronic pain development after surgery likely occurs as a result of complex biochemical and pathophysiologic mechanisms which will differ in type among different surgical procedures.  This article focuses on how postoperative, traumatic, and neuropathic nociception are generated and interrelated, with the goal of providing a deeper understanding of how long-term pain develops so that we can prevent and treat it more effectively. An emphasis is placed on areas of current interest, however, with a problem as complex as chronic pain, it will inevitably generate more questions than it answers, in the hope of stimulating more research and inquiry.

Mechanism for Acute Pain Generation ( 1: Peripheral effects, 2:Spinal/Central effects (Neuroplascity))

The generation of acute pain can be summarized in the following way. Surgery-associated tissue injury is interpreted neuraxially in the same way as trauma-associated injury. Pain sensation varies according to the intensity, quality and duration of stimuli. Surgery sets off a cascade of interrelated events designed to fight infection, limit further damage and initiate repair.  It involves nociception, in addition to inflammation, and nerve cell remodeling. Proinflammtory cytokines, chemokines, and neurotrophins induce both peripheral and central nerve sensitization to heighten pain awareness in order to limit further injury to the affected area. In the generation of pain, multiple pain systems are known to be activated.

It is the activation of nociceptors in the periphery, and their ongoing activation, through processes such as peripheral and ultimately central sensitization, that underlies one mechanism of the transition to the chronic pain state. Nociceptors are free nerve endings, with no extracellular matrix capsule or epithelial cell adjoined to the neurone, and respond to stimuli that damage or threaten to damage tissue. Nociceptors are present in skin, muscle, joints, and viscera, with varying degrees of density. It is this density of population which allows for our differential sensatory ability; for example, the ability to discern the spatial resolution of the application of two separate pin pricks on a finger tip compared withthe skin overlying the back.  These nociceptors are the primary afferent terminals of nerves that generate impulsesto the spinal cord, and are categorized by both their type of stimulation, and by their response to that activation.

A-δ fibres are fast conducting myelinated nerves. These fibres are activated by heat via mechanothermal receptors (MTRs), and high threshold mechanoreceptors (HTMs). The degree of the stimulus is translated into a proportional intensity of firing in these fibres.

In contrast, C-fibres are unmyelinated, slow conducting fibres, with receptive fields smaller than those of A-δ nociceptors. In the non-sensitized state, they also have higher thresholds for activation compared with A-δ fibres or A-β fibres. These fibres represent the majority of peripheral nociceptors, and most are of the C-polymodal neuronetype (C-PMN). Like the A-δ fibres, C-fibres respond to thermal and mechanical stimulation. However, unlike the A-δ fibres, they also respond to chemical stimuli, and produce sensation consistent with itching.

A-β fibres are large diameter and highly myelinated, and only convey proprioception and touch.

Nociceptors are either specific to the type of noxious stimuli they respond, or are wide dynamic range (WDR) nociceptors, in which they respond to a continuum of stimuli, such as the sensation of light pressure up to a crushing stimulus.^[a] By varying both in their threshold to stimuli and their rate of firing to the dorsal horn, action potential processing into the CNS can span a wide range of pain perceptions, both in quality and intensity. Furthermore, by responding differently to stimuli, these nociceptors allow us to experience a wide range of sensory phenomenon.A-δ and C-fibre trafficking to the dorsal horn terminates superficially in laminae I-II, with a few connections to deeper laminae, whereas A-β fibres predominantly traffic to laminae III-VI[4]. Centrally, within the laminae of the dorsal horn, receiving neurones are either specific to either A-δ and C-fibres, or A-β input, or are wide dynamic range neurones receiving input from all three. These second order neurone connections can be influenced by both excitatory glutamatergic and inhibitory GABAergic interneurones, or by astrocytes and microglia, particularly under pathologic states. Furthermore, within lamina I approximately 80% of these cells express the neurokinin 1 (NK1) receptor for substance P, and it is these cells that have been shown to project to the thalamus, PAG, and the parabrachial area (PB). Hence, lamina I cells play a strong role in the inhibitory and facilitatory descending pathways from higher CNS centers[5].

The CNS can alter the afferent nociceptive information it receives by a descending or modulatory system. This system arises out of several regions of the CNS, including the somatosensory cortex, hypothalamus, periaquaductal gray, pons, lateral tegmental area, and raphe magnus. These structures communicate with laminae I and V via the dorsolateral funiculus. Stimulation of these areas, or of their common outlet path via the dorsolateral funiculus, causes a blunting or inhibition of nociceptive impulses promoting an analgesic effect [6]. Descending inhibition largely involves the release of norepinephrine (NE) in the dorsal horn from the locus coeruleus(LC), acting at the α2-adenoceptor subclass, and inhibiting primary afferent terminals and suppressing firing of projection neurones[7-8].