Sympathetic nervous system and pain: pathophysiological mechanisms

Abstract

Sympathetic postganglionic neurons may be involved in the generation of pain, hyperalgesia and neurogenic inflammation under pathophysiological conditions. Experiments on animal models show that two categories of influence of the sympathetic neuron on afferent neurons can be distinguished and this distinction seems to be related as to whether sympathetic-afferent coupling develops after nerve lesion or after tissue trauma with inflammation. (1) Peripheral nerve lesion generates plastic changes of the afferent and sympathetic postganglionic neurons. This may lead to chemical coupling between sympathetic and afferent neurons which may entail activation and/or sensitization of primary afferent neurons by the sympathetic neurons. The mediator is probably noradrenaline and the afferent neuron expresses or upregulates functional adrenoceptors. The coupling may occur at different sites of the primary afferent neuron, e. g., at the lesion site, remote from the lesion site in the dorsal root ganglion or between nonlesioned sympathetic and afferent neurons which show collateral sprouting. The biochemical signals which trigger these changes probably are neurotrophic substances and their receptors which are synthesized by the peripheral neurons, Schwann cells and other cells in response to the peripheral lesions. (2) Sympathetic nerve terminals in peripheral tissues may serve as mediator elements in hyperalgesia and during inflammation following tissue trauma without nerve lesion. This function is largely independent of activity in the sympathetic neurons and independent of vesicular release of transmitter substances. The signals are probably synthesized and released from the sympathetic terminal or in association with it and belong to the prostaglandins (probably PGE(2) or PGI(2)). Furthermore, nerve growth factor (NGF) has a hyperalgesic action in inflammation which is at least in part dependent on the sympathetic nervous system.