Endogenous descending modulation: spatiotemporal effect of dynamic imbalance between descending facilitation and inhibition of nociception

In conscious rats, we investigated the change of nociceptive paw withdrawal reflexes elicited by mechanical and heat stimuli during intramuscular (i.m.) 5.8% hypertonic (HT) saline elicited muscle nociception. i.m. injection of HT saline caused rapid onset, long lasting (around 7 days), bilateral mechanical hyperalgesia, while it induced bilateral, slower onset (1 day after the HT saline injection), long‐term (about 1–2 weeks) heat hypoalgesia. Ipsilateral topical pre‐treatment of the sciatic nerve with 1% capsaicin significantly prevented the occurrence of both the bilateral mechanical hyperalgesia and the contralateral heat hypoalgesia. Intrathecal administration of either 6‐hydroxydopamine hydrobromide (6‐OHDA) or 5,7‐dihydroxytryptamine (5,7‐DHT), and intraperitoneal injection of naloxone all markedly attenuated the HT saline induced bilateral heat hypoalgesia, but not the mechanical hyperalgesia. Combined with experiments with lesioning of the rostroventral medulla with kainic acid, the present data indicate that unilateral i.m. injection of HT saline elicits time‐dependent bilateral long‐term mechanical hyperalgesia and heat hypoalgesia, which were modulated by descending facilitatory and inhibitory controls, respectively. We hypothesize that supraspinal structures may function to discriminate between afferent noxious inputs mediated by Aδ‐ and C‐fibres, either facilitating Aδ‐fibre mediated responses or inhibiting C‐fibre mediated activities. However, this discriminative function is physiologically silent or inactive, and can be triggered by stimulation of peripheral C‐fibre afferents. Importantly, in contrast to the rapid onset of descending facilitation, the late occurrence of descending inhibition suggests a requirement of continuous C‐fibre input and temporal summation. Thus, a reduction of C‐fibre input using exogenous analgesic agents, i.e. opioids, may counteract the endogenous descending inhibition. Endogenous descending modulation (inhibition/facilitation) is important to govern pain and nociception in humans as well as animals. We show that supraspinal structures have a function to discriminate responses evoked by activation of different subgroups of afferents, and in turn either excite Aδ‐fibre mediated responses or inhibit C‐fibre mediated activities. Importantly, the initiation of descending modulation is dependent of sufficient afferent signals mediated by C‐fibres. Improved neurobiological and neurophysiological knowledge of endogenou