Morphine Self-Administration following Spinal Cord Injury

Abstract

Neuropathic pain develops in up to two-thirds of people following spinal cord injury (SCI). Opioids are among the most effective treatments for this pain and are commonly prescribed. There is concern surrounding the use of these analgesics, however, because use is often associated with the development of addiction. Previous data suggests that this concern may not be relevant in the presence of neuropathic pain. Yet, despite the common prescription of opioids for the treatment of SCI-related pain, there has been only one previous study examining the addictive potential of morphine following spinal injury. To address this, the present study used a self-administration paradigm to examine the addictive potential of morphine in a rodent model of SCI.Animals were placed into self-administration chambers 24 h, 14 d, or 35 d following a moderate spinal contusion injury. They were placed into the chambers for seven 12-hour sessions with access to 1.5 mg morphine/lever depression (up to 30 mg/d). In the acute phase of SCI, contused animals self-administered significantly less morphine than their sham counterparts, as previously shown. However, contused animals showing signs of neuropathic pain did not self-administer less morphine than their sham counterparts when administration began 14 or 35 d after injury. Instead, these animals administered nearly the full amount of morphine available each session. This amount of morphine did not affect recovery of locomotor function but did cause significant weight loss. We suggest caution is warranted when prescribing opioids for the treatment of neuropathic pain resulting from SCI, as the addictive potential is not reduced in this model.

Neurobiological Effects of Morphine after Spinal Cord Injury

“…Commensurate with previous studies, 7,8,30 both surgery and morphine administration significantly affected weight gain (Fig. 3).…”

“…There was a significant increase in the lesion size of morphine-treated subjects, and replicating our previous studies, we found that morphine significantly undermined recovery of locomotor function after SCI. [5][6][7][8]30 Despite the loss of neurons, however, repeated morphine administration led to the development of opioid-induced hyperalgesia, with subjects displaying increased reactivity to innocuous mechanical stimulation. As suggested by Garraway and associates, 29 a loss of GABAergic neurons after SCI, and morphine in the current study, may underlie this paradoxical pain hypersensitivity.…”

“…To allow for the administration of morphine, all subjects were implanted with a jugular catheter. 8,30 Rats were anesthetized using a combination of ketamine 80 mg/kg and xylazine 10 mg/kg intraperitoneally (IP). While under anesthesia, a catheter consisting of a length of PE50 tubing was inserted into and tied to the jugular vein.…”

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.…”