Dose-dependent antinociceptive response of morphine microinjected into the nucleus cuneiformis andeffect of inactivation of this area on pain modulation in rat

The cuneifo rmis nu cle us (CnF) is o ne of th e re t icu lar fo rmation e nti ties which rests in midbrain region. Th is nucle us co nt ro ls pain indi rec tly thro ugh its binding with rostr al ve ntromedi al medulla (RVM). From previous res ea rches, it's been pr oved th at th is nucleus has ult rastructural similarities and bidir ec tio nal connections with pe riaq ueductal gray (PAG) matt er. In present study, in according to these similarities and connections, we tried to know the antinociceptive response of morphine microinjected into the nucleus cuneiformis and effect of inactivation of this area on pain modulation. Rats were pl aced in ste reotaxic instrument, with a hole being drilled over cerebellum on skull and a guide cannula was forced down just 1 mm above the CnF. Followin g surgery and re cove ry period, vario us doses of morphine (10, 20 and 40}Lg/0.5}Ll saline) and lidocaine 5% (0.5}Ll) were microinjected into the CnF. Tail Flick Latency (TFL) and Maximal Possible Effect (%MPE) were measu red 30 min in 5-min interva ls, before and afte r any injection as an index for nociceptive responses. Naloxone was injec ted intravenously to exactly pinpoint morphine action as a non -selective antago nist. Morphine increased TFL in a dose dependent manner. Also inactivation of CnF by lidocaine inc reased TFL. Simultaneously micro injection of morphine and lidoc ai ne inc reased TFL which was le ss th an morph ine effect (%MPE) alone. While inje ct in g mo rphine intravenouslywith lidocain e microinjection increased significa ntly TFL bu t th ese effects were reversed by naloxone administration. It is clear that CnF has opioid receptors, specially}L receptor, that follow in a dose dep endent manner. On th e ot her han d, we suggest th at CnF inactivation with lidocaine inhib its a n inhibitory o utput tha t pr oject s to RVM specially off-cells in t his area and th is disinhibition causes pain modulation.