پاسخ ضد دردي وابسته به دوز مرفين تزريق شده در هسته ميخي شكل و تاثير غيرفعال كردن اين ناحيه بر تعديل درد در موش صحرايي

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

Introduction: The cuneiformis nucleus (CnF) is one of the reticular formation entities which rests in midbrain region. This nucleus controls pain indirectly through its binding with rostral ventromedial medulla (RVM). From previous researches, itʹs been proved that this nucleus has ultrastructural similarities and bidirectional connections with periaqueductal gray (PAG) matter. 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. Materials and Methods: Rats were placed in stereotaxic instrument, with a hole being drilled over cerebellum on skull and a guide cannula was forced down just 1 mm above the CnF. Following surgery and recovery period, various doses of morphine (10, 20 and 40 ^g/0.5 /xl saline) and lidocaine 5% (0.5 fjA) were microinjected into the CnF. Tail Flick Latency (TFL) and Maximal Possible Effect (%MPE) were measured 30 min in 5-min intervals, before and after any injection as an index for nociceptive responses. Naloxone was injected intravenously to exactly pinpoint morphine action as a non-selective antagonist, Results: Morphine increased TFL in a dose dependent manner. Also inactivation of CnF by lidocaine increased TFL. Simultaneously microinjection of morphine and lidocaine increased TFL which was less than morphine effect (%MPE) alone. While injecting morphine intravenously with lidocaine microinjection increased significantly TFL but these effects were reversed by naloxone administration. Conclusion: It is clear that CnF has opioid receptors, specially fi receptor, that follow in a dose dependent manner. On the other hand, we suggest that CnF inactivation with lidocaine inhibits an inhibitory output that projects to RVM specially off-cells in this area and this disinhibition causes pain modulation.