Papers of the Week

Spinal α-adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to G proteins can be subdivided into three functional subtypes: α, α and α-adrenoceptors, and current evidence on spinal analgesia supports the relevance of α and seems to exclude the role of α, but the functional contribution of α-adrenoceptors remains elusive. The present study was designed to pharmacologically dissect the contribution of spinal α-adrenoceptor subtypes modulating tonic or acute peripheral nociception. Using male Wistar rats, we analyzed the effect of spinal clonidine (a non-selective ααα-adrenoceptor agonist) and/or selective subtype α-adrenoceptor antagonists on: 1) tonic nociception induced by subcutaneous formalin (flinching behavior) or 2) acute nociception induced by peripheral electrical stimulus in extracellular recordings of spinal dorsal horn second-order wide dynamic range (WDR) neurons. Clonidine inhibited the nocifensive behavior induced by formalin, an effect blocked by BRL 44408 (α-adrenoceptor antagonist) but not by imiloxan (α-adrenoceptor antagonist) or JP 1302 (α-adrenoceptor antagonist). Similarly, spinal BRL 44408 reversed the clonidine-induced inhibition of nociceptive WDR activity. Interestingly, spinal JP 1302 produced behavioral antinociception (an effect blocked by bicuculline, a preferent GABA channel blocker), but no correlation was found with the electrophysiological experiments. These data imply that, at the spinal level, 1) presynaptic α-adrenoceptor activation produces antinociception during acute or tonic nociceptive stimuli; and 2) under tonic nociceptive (inflammatory) input, spinal α-adrenoceptors are pronociceptive, probably by the inactivation of GABAergic transmission. This result supports a differential role of α and α-adrenoceptors modulating nociception.