ANTIALLODINIC AND ANTIHYPERALGESIC EFFECTS OF LP1, AN OPIOID MULTITARGET LIGAND, IN INFLAMMATORY AND NEUROPATHIC PAIN STATES

Persistent pain states, such as those caused by nerve injury or inflammation, are characterized by an altered transmission and modulation of nociceptive stimuli (1). Despite opioid agonists are the cornerstones of treatment of moderate-to-severe acute pain, their effectiveness for chronic pain management is controversial (2). It has been proved that multitarget opioid ligands, produce an enhanced antinociceptive effect coupled to a low incidence of undesirable effects. The antinociceptive agent LP1, a benzomorphan-based compound, proved to be as potent as morphine in an acute pain protocol acting as a good MOR agonist also able to counteract DPDPE-mediated analgesia. Administration of naloxone methiodide, showed that central opioid receptors were prevalently involved in the antinociceptive effect of LP1 that, chronically administered, displayed a low tolerance-inducing capability (3). Our efforts were focused on role of LP1 on thermal hyperalgesia and mechanical allodynia, two typical signs of persistent pain. To this aim LP1 was tested in a model of neuropathic pain induced by chronic constriction injury of the left sciatic nerve, and inflammatory pain produced by intraplantar injection of carrageenan. In both conditions subcutaneous LP1 determined a significant antiallodynic effect, measured with von Frey filaments, and antihyperalgesic effect, evoked in response to plantar test. Thus the multitarget opioid compound LP1, with its MOR agonist-DOR antagonist properties, could be a promising drug for the treatment of chronic pain states.