Role of low-intensity laser therapy on naloxone-precipitated morphine withdrawal signs in mice: is nitric oxide a possible candidate mediator?

In the present study, the potential involvement of nitric oxide (NO) system in attenuating effects of low-intensity laser therapy (LILT) on naloxone-induced morphine withdrawal signs was evaluated. A hundred mice were rendered morphine-dependent using three escalating doses of morphine sulfate during three consecutive days. After the last dose on day 4, animals were given naloxone HCl (2 mg/kg s.c) to induce withdrawal signs. The effects of LILT (12.5 J/cm²) and l-NG-nitroarginine methyl ester (l-NAME) (10, 20, 50, and 100 mg/kg) and their coadministration on escape jump count and stool weight as typical withdrawal signs were assessed. LILT and l-NAME (20, 50, and 100 mg/kg) per se significantly decreased escape jump count and stool weight in morphine-dependent naloxone-treated mice (p < 0.01). Coadministration of LILT and l-NAME (20, 50, and 100 mg/kg) also reduced escape jump and stool weight (p < 0.05) but with no synergetic or additive response. Here, LILT at this fluence may show its maximal effects on NO and therefore no noticeable effects appeared during coadministration use. Moreover, LILT and l-NAME follow the same track of changes in escape jump and stool weight. Conceivably, it seems that LILT acts partly via NO system, but the exact path is still obscure and rather intricate. The precise mechanisms need to be clarified.