Coeruleospinal inhibition of nociceptive processing in the dorsal horn during unilateral hindpaw inflammation in the rat

Abstract

Behavioral and neurochemical studies have shown that the coeruleospinal modulation system is activated by peripheral inflammation, and that this modulation system is active in only the dorsal horn ipsilateral, but not in the dorsal horn contralateral, to the site of inflammation; the present study was designed to confirm electrophysiologically this previous finding. Extracellular recordings from dorsal horn neurons were continued for at least 4 h after the induction of inflammation. Unilateral hindpaw inflammation was produced by a subcutaneous injection of carrageenan (2 mg in 0.15 ml saline). Background activity and responses to noxious heating were compared between rats receiving bilateral lesions in the locus coeruleus/subcoeruleus (LC/SC) and non-operated control rats. In neurons located in the dorsal horn ipsilateral to the inflamed paw, prior to inflammation, there was no significant difference in either the background activity or the heat-evoked response in neurons in LC/SC-lesioned compared to LC/SC-intact rats. Four hours after the induction of inflammation, there was a significant increase in both the background activity and heat-evoked response in neurons in LC/SC-lesioned compared to LC/SC-intact rats. In neurons located in the dorsal horn contralateral to the inflamed paw, 4 h after inflammation, no significant increase in either the background activity or the heat-evoked response in neurons in LC/SC-lesioned rats was observed, as well as in the case before inflammation. These results suggest that the coeruleospinal modulation system is active in only the dorsal horn ipsilateral, but not in the dorsal horn contralateral, to the site of inflammation during the development of unilateral hindpaw inflammation.

Inflammation-Induced Enhancement of the Visceromotor Reflex to Urinary Bladder Distention: Modulation by Endogenous Opioids and the Effects of Early-in-Life Experience With Bladder Inflammation

“…Similar views have been advanced to account for the loss of spinal morphine suppression of somatic nociception and tactile allodynia following tight ligation of L5/L6 nerves. 24 There also is abundant evidence that descending inhibitory systems derived from either the rostroventral medulla (RVM) 11,32 or the locus coeruleus (LC) [33][34][35][36] are recruited following inflammation of somatic tissue. While these descending systems are present at birth, they are only partially functional by P10-P12 and become functionally mature by P21.…”

“…26 This enhanced bladder response was paralleled by a more global bladder hypersensitivity, manifested as increased micturition frequency 26 and decreased thresholds for micturition reflexes during cystometry. 8 Other studies of primary hyperalgesia and inflammation involving either the knee joint 31 or the hindpaw 28,39 have shown that descending inhibitory systems are progressively engaged during the first 24 hrs of acute inflammation and act to suppress somatic hyperalgesia (see also 11,27,[32][33][34][35][36] ). These data suggested the possibility that the urinary bladder hypersensitivity produced by acute bladder inflammation in the adult rat may be concomitantly suppressed by inflammation-induced activation of an inhibitory system 37,38 and that the enhancement effect we observed with neonatal exposure to zymosan might be due to impairment of this inhibitory system.…”

A possible synaptic configuration underlying coeruleospinal inhibition of visceral nociceptive transmission in the rat

“…Previously, we suggested that a possible role of the coeruleospinal modulation system is to provide a means to discriminate differences in the intensity of a painful stimulus applied to the body region in the persistent pain state, as well as to the normal body region [18]. In this context, presynaptic inhibition may be advantageous for maintaining the accuracy of intensity coding in the dorsal horn because gain reduction that is due to presynaptic inhibition results in decreased output from dorsal horn neurons.…”

A possible role of the locus coeruleus in complex regional pain syndrome

“…In rats, coeruleospinal pain modulation appears to be active in the dorsal horn ipsilateral, but not contralateral, to the site of paw inflammation (Tsuruoka et al, 1999, 2003, 2004). Moreover, the inhibitory influence extends beyond the involved segment to distant ipsilateral segments.…”