Substance P reduces tail-flick latency: Implications for chronic pain syndromes

Publisher Website
Google Scholar
Abstract
In the awake restrained rat the intrathecal administration of substance P or the partial substance P homolog eledoisin-related peptide (ERP) reduced reaction time to a noxious radiant heat stimulus and, at high doses, produced additional behavioral responses suggesting that the animals had reacted to what they perceived as a painful stimulus. The reduction in tail-flick latency was observed as early as 30 s following peptide administration peaked at 1 min and persisted for 5-10 min, after which an overshoot of the response (i.e., an increase in reaction time) was observed. The responses varied in their magnitude with the amount of peptide given, substance P being .apprx. 4 times more potent on a molar basis than ERP. Intrathecal administration of an equal volume of vehicle (artificial CSF) had no effect on tail-flick latency and failed to produce any of the other behavioral changes. The decrease in tail-flick latency suggests that pain threshold was decreased, and the dramatic behavioral effects seen at high doses suggest that an excess of substance P in the spinal cord is capable of producing a painful sensation. The rapid onset of the response suggests rapid penetration of substance P and ERP to the appropriate receptors, and the rapid decay of the response suggests rapid removal. Substance P probably plays a role as an excitatory agent in sensory pathways subserving pain. Some conditions of chronic pain in man may be due to an overabundant amount of substance P. This complements a 2nd proposal that other cases of chronic pain may be due to a supersensitivity of substance P receptors. The former is more likely to be associated with organic disorders, the latter with nerve damage, e.g., with causalgia, the neuralgias and perhaps some cases of phantom limb pain.