Neuroscience
-
Cloning studies have identified a novel seven transmembrane receptor displaying high sequence homology to the three classical opioid receptors (mu, delta and kappa). This receptor is widely distributed throughout the CNS. 1 Recently, an endogenous ligand for this receptor was isolated (termed either "orphanin FQ" or "nociceptin") and identified as a heptadecapeptide showing sequence homology with the endogenous opioids. Surprisingly, in contrast to known opioids, orphanin FQ displays hyperalgesic rather than analgesic properties. ⋯ These preliminary data suggest that orphanin FQ systems may act in an opposing manner to the previously well-described enkephalin and endorphin systems. Since numerous studies have implicated activation of the mesolimbic dopamine pathway to be central to the rewarding actions of opiates such as morphine and heroin, as well as several other abused drugs, and also to mediate the hyperlocomotory action of such drugs, we sought to determine the effect of orphanin FQ on this pathway. In accordance with the inhibitory effect of this peptide on locomotor activity, we now report that orphanin FQ suppresses dopamine release in the nucleus accumbens in a dose-dependent manner, providing the first neurochemical evidence for a modulatory role of this recently described peptide in the CNS.
-
The heptadecapeptide orphanin FQ has recently been shown to be the endogenous agonist for the orphan opioid-like receptor, LC132. The molecular evidence that LC132 and orphanin FQ are evolutionarily related to other opioid receptors and their ligands suggests that these proteins may also play a role in modulating opiate actions. ⋯ In addition to its antagonism of endogenous opioid antinociception, orphanin FQ dose-dependently (2.5-25 nmol) reverses systemic morphine antinociception (5 mg/kg, s.c.). Based on these data, we propose that orphanin FQ is a functional anti-opioid peptide.
-
Autotomy in experimental animals following peripheral nerve section has been interpreted as a sign of pain corresponding to the chronic pain observed in patients with extensive nerve lesions. Such pain may be alleviated by spinal cord stimulation. In the present study, the effect of such stimulation, via chronically implanted electrodes, on autotomy behavior following sciatic nerve section was assessed in the rat. ⋯ It seems that spinal cord stimulation, albeit applied only once daily and during a limited time period, can protect the spinal cord from developing the state of hyperexcitability believed to be the major cause of autotomy behavior. Peripheral mechanisms may also play a role by the antidromic activity evoked by the stimulation in the sectioned peripheral nerve. This study shows that spinal cord stimulation, which is a commonly employed method for treating chronic neurogenic pain, may have long-lasting effects on plasticity changes in the spinal cord following peripheral nerve injury, even when the stimulation is applied for short periods of time.