The Role of the Spinal Opioid Receptor Like1 Receptor, the NK-1 Receptor, and Cyclooxygenase-2 in Maintaining Postoperative Pain in the Rat

Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision

“…It was unclear, however, how SP participates in models of incisional pain. Earlier pharmacological testing has implicated the NK-1 SP receptor in post-incisional sensitization [25]; [62]. Consistent with those reports the present study demonstrated that the ppt-A (−/−) mice exhibit deficits in both heat and mechanical nociceptive signaling in the incisional model.…”

Spinal Glial Activation Contributes to Postoperative Mechanical Hypersensitivity in the Rat

“…For example, although spinal N-methyl-D-aspartate (NMDA) receptor antagonists attenuate hypersensitivity in most models of persistent pain, they are not effective after surgical incision. 27 In contrast, intrathecal administration of non-NMDA receptor antagonists, 28 NK-1 receptor antagonists, 26 and cyclooxygenase-1 inhibitors effectively reduces incisional hypersensitivity while having little effect on nerve injury-induced pain. 30 Furthermore, although descending facilitation from rostral ventromedial medulla contributes to behavioral hypersensitivity of diverse animal models of inflammatory and neuropathic pain, 17 this mechanism is not involved in the hypersensitivity after incision.…”

Cyclooxygenase-2 inhibition potentiates morphine antinociception at the spinal level in a postoperative pain model

“…3 Therefore, it is not evident why spinal L-745,337 alone does not reduce postoperative pain, although another COX-2 inhibitor, NS398, has also been shown ineffective intrathecally. 10 The exact mechanism by which a COX-2 inhibitor can modulate -opioid activity in the spinal cord has not been determined. There is analgesic synergy between the NSAID ketorolac and morphine given intrathecally in the rat hindpaw formalin test.…”

“…Using a rat foot-incision model, 9 intrathecal COX-2 inhibitors administered alone had a minimal effect in attenuating mechanical hyperalgesia. 10 However, there are clinical studies showing a morphine-sparing effect of NSAIDs in postoperative pain, 11 and, more recently, COX-2 inhibitors administered before orthopedic surgery reduced postoperative opioid use. 12 Therefore, the optimal strategy for using COX-2 inhibitors intrathecally to modulate postoperative pain may be in combination with opiates.…”