Combinations of haloperidol and morphine produce maximal levels of anti‐hyperalgesic or potentiation effects in rats with neuropathic pain

Abstract

Neuropathic pain (NP) is a chronic disorder that result from an injury or dysfunction at central or peripheral nervous system, promoting alterations in control and modulation of nociceptive signalling pathways. The haloperidol is a butyrophenone prototype, that recently some authors have described as anti‐nociceptive drug mediated by sigma‐1 receptors antagonism. Besides, morphine is a prototype analgesic opioid drug currently used in the NP treatment.ObjectiveTo detect the optimal combinations generated by therapy of haloperidol with morphine in NP induced by chronic constriction injury (CCI).MethodsThe anti‐hyperalgesic effects of haloperidol (0.017–0.100 mg/Kg, s.c.) and morphine (0.01–3.16 mg/Kg, s.c.) were determined after single‐doses, both in monotherapy and combined, using the von Frey test. Evaluations were done until 10 days post‐surgery at 30, 60, 90, 120 and 180 minutes after drugs administration and data were processed using Surface of Synergic Interaction analysis (SSI).ResultsHaloperidol and morphine showed a dose‐dependent anti‐hyperalgesic effects. From 16 combinations studied, six were potentiation, while remaining 10 combinations resulted in an additive effect or limited by the maximum effect of the individual doses. The combination morphine (0.0316 mg/Kg) and haloperidol (0.01778 mg/Kg) showed the maximum potentiation effect (p<0.001). In turn, the combination of maximum anti‐hyperalgesic efficacy (p<0.01) was morphine (1.0 mg/Kg) and haloperidol (0.1 mg/Kg). Interestingly, was detected that is required a haloperidol single dose tenfold higher than haloperidol dose employed by the combination of maximum potentiation for reach similar antinociceptive effect.ConclusionsThis study showed that haloperidol and morphine in combination can produce addition and potentiation effects in neuropathic pain, and the SSI analysis allowed to detect the optimal combinations to produce maximum efficacy or maximum potentiation of anti‐hyperalgesic effects.Support or Funding InformationDepartment of Pharmacobiology, Cinvestav‐Unidad Coapa, C.P. 14330, Tlálpan, Mexico City, Mexico.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.