Involvement of a Descending Pathway from the A7 Region in Nociceptive Processing under Neuropathic Conditions in Rats

Abstract

The A7 cell group in the dorsolateral pons provides noradrenergic innervation of the spinal cord. Activation of this descending pathway (the A7 descending system) produces bi-directional effects on nociceptive processing in the dorsal horn, which are facilitation mediated by α1-adrenoceptor and inhibition via α2-adrenoceptor. Peripheral nerve injury sometimes results in neuropathic pain. Hypersensitivity of dorsal horn neurons under neuropathic conditions is linked to activity in descending pathways from the brain. The aim of this study was to examine the involvement of the A7 descending system under neuropathic conditions. Experiments were performed on male Sprague-Dawley rats (n=35). Bilateral lesions of the A7 area were performed by microinjection of kainic acid. The tibial and common peroneal the nerves were sectioned produce neuropathic conditions (spared nerve injury, SNI). For estimating mechanical allodynia, mechanical hypoalgesia and cold allodynia, paw withdrawal threshold (PWT), paw withdrawal latency (PWL) and paw withdrawal frequency (PWF) were measured. PWTs significantly decreased following A7 lesions. After SNI, PWTs signifi cantly decreased in A7-lesioned and sham-lesioned rats. However, no signifi cant difference was observed between the decreased rates of PWTs in A7-lesioned and sham-lesioned rats. PWLs signifi cantly increased in sham-lesioned rats compared with A7-lesioned group. PWFs signifi cantly increased in the A7-lesioned and sham-lesioned rats. Intrathecal injection of prazosin, an α1-adrenoceptor antagonist, failed to change the PWT, PWL and PWF in non-A7-lesioned neuropathic rats. These results suggest that (1) the A7 descending inhibitory system has tonic activity under normal conditions, and (2) this system functions in a complex manner during the neuropathic pain state.