Neurophysiological effects of capsaicin

Data obtained from neonatally treated rats are fairly consistent. However, there is disagreement as to whether mechanical and thermal nociceptive thresholds are elevated or unchanged in this group. There are at least two major areas of disagreement in adult animal capsaicin research. Behavioral data are extremely variable. The thermal nociceptive threshold after systemic capsaicin has been reported to be both raised and lowered. After intrathecal capsaicin injection, the thermal nociceptive threshold was reported raised, but onset and duration of responses varied and some animals exhibited no changes. Capsaicin application to peripheral nerve, however, drastically increased thermal threshold. Mechanical pain threshold has been reported both increased and unchanged after systemic capsaicin treatment and unchanged after intrathecal injection. Obviously, capsaicin's effects upon pain perception are not fully understood. Although lower on the phylogenetic scale than many mammals, rodents exhibit complex individualistic behavior. Lower vertebrates may eventually provide more simple behavioral models for pain tolerance. Investigators also disagree as to whether C fibres can conduct action potentials after local capsaicin application. C fibre conduction was reported unaffected by capsaicin in an acute preparation and for 13-21 days after treatment. On the other hand, C fibre compound action potentials have been reported diminished for up to 2 h after capsaicin application. Additional conduction impairment studies will be useful in comparing peripheral and intrathecal capsaicin application. There is general agreement that, allowing for variation in dosages and route of administration, capsaicin causes central and peripheral C fibre damage, though never as extensive in adults as in neonates. Neonatal capsaicin treatment (always s.c.) results in destruction of C and some Aδ fibres and their central terminals. Capsaicin causes degeneration of C terminals in the adult CNS only when applied centrally. In both neonates and adults, s.c. capsaicin depletes the putative 'pain' peptide neurotransmitter, SP, from peripheral and sensory neurons and the tissues they innervate but not from the gut. Capsaicin-induced SP depletion in neonates is permanent. Systemic administration to adult depleted SP from much the same areas as observed in neonates, but all areas but the medulla exhibited a slow, regional recovery. Intraventricular injection of capsaicin depleted SP in the adult medulla only, while other SP-containing areas affected by systemic injection remained intact. Intranigral capsaicin injection had no effect on SP content but depleted 5-HT and its metabolite, 5-HIAA, and dopamine metabolites. Direct application of capsaicin to the sciatic nerve may block axonal peptide transport in sensory C fibres but not in motor fibres. In neonates, capsaicin depleted peptide markers of primary afferents, i.e., SRIF, VIP, CCK, FRAP, GABA and opiate receptors from the spinal cord and/or DRG. Systemic administration to adults depleted SRIF and FRAP in the dorsal spinal cord but not opiate receptors or glutamic acid decarboxylase (GAD) activity. Probably because of capsaicin-induced structural and biochemical alterations, spinal, medullary, and peripheral neurons become at least temporarily less responsive, although not uniformly so. Neonatal capsaicin treatment abolished the C fibre mediated neurogenic oedema response to injury or irritation. Subcutaneous administration or direct (but not intrathecal) application of capsaicin to peripheral nerve temporarily blocked neurogenic oedema in adults. On a gross scale, pharmacological tests employing capsaicin are aimed at identifying the receptors it affects to explain complex visceral reflex mechanisms. Neurophysiological tests are more specific because so far, capsaicin has been found to affect only nociceptive primary afferents. At the cellular level, capsaicin depolarizes sensory terminals and exerts a Ca²⁺ dependent SP release in the spinal cord. Capsaicin prolongs sensory neuron action potentials, whereas opiates and opioid peptides shorten AP duration and inhibit SP release from spinal sensory terminals. Capsaicin's hyperpolarization of DRG neurons provides an interesting contrast that indicates differences in its effects on ganglionic, axonal, terminal and receptor sites. Also due to its specific action, capsaicin has been used to indicate presynaptic opiate receptors on SP-releasing spinal nociceptive terminals.