Neurobiology of chronic pain states

Abstract

In chronic pain states there are major changes in the peripheral and central nervous system. These are dynamic, responding to changes in input and displaying significant alterations over time. This article outlines some of the changes found peripherally, at the level of the spinal cord and in the brain, focussing on neuropathic pain. Peripherally, action potentials arise spontaneously at sites distant from peripheral nociceptors. These ectopic discharges are found at the nerve injury site and at the dorsal root ganglia. They may contribute to the generation of spontaneous pain. Peripheral nerves also show an increased responsiveness to stimulation as mechanosensitive areas appear on the nerves. Both these phenomena may be related to changes in sodium channel subtypes. The general increase in primary afferent drive is likely to contribute towards changes occurring in the spinal cord. In the spinal cord, degeneration of central primary afferent terminals occurs with subsequent trans-synaptic degeneration of intrinsic spinal neurons. Major changes are seen in the neurotransmitters synthesized and released by primary afferent neurons. Central sensitization with an increase in the effect of glutamate is seen, involving a variety of glutamate receptor subtypes, including the NMDA receptor. Brainstem systems modulate spinal input, facilitating onward transmission, with a reduction in tonic inhibitory control normally exerted by some of these systems. Cortical processing also changes in some chronic pain states. The challenge to clinicians is whether improved understanding of neurobiology can be translated into prevention or more effective treatment of chronic pain.