The impact of morphine after a spinal cord injury

Abstract

Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20 mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20 mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury.

Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation

“…Secondly, opioids superimposed on CNS neuroinflammation may have far-ranging consequences beyond pain. For example, opioids may also serve as a second hit for glia primed by aging or inflammation/trauma and may lead to cognitive decline in the elderly (63), postoperative cognitive decline (64), and impaired recovery of motor function after spinal cord injury (65,66). Whether the mechanistic underpinnings revealed in the current series of studies will prove to generalize to such opioid-related phenomena remains to be defined.…”

Nor-Binaltorphimine Blocks the Adverse Effects of Morphine after Spinal Cord Injury

“…[1][2][3][4][5] To address this, norBNI was administered as an adjuvant to morphine treatment 24 h following SCI, and locomotor recovery was monitored for a 21 day period. Locomotor scores collected before treatment on day 1 did not differ significantly across groups (F [7, Fig.…”

“…[1][2][3][4][5] As opioids are currently among the most effective analgesics for the treatment of pain in the acute phase of SCI, it is essential that we identify the mechanisms underlying these adverse side effects and improve the safety of these medications.…”

Long-term Follow-up of Cutaneous Hypersensitivity in Rats with a Spinal Cord Contusion

“…Recently, experiments to elucidate the underlying mechanisms of pain and potential therapeutic intervention have been done using this model (Hook et al, 2007;Lee et al, 2007;Voda et al, 2007;Zhao et al, 2007). Even though SCI-induced pain may last for a long period of time and remission of pain has been reported to be rare in human patients (Stormer et al, 1997), experimental studies on animals were done mainly between 3 to 6 weeks after SCI.…”