The Efficacy of Intrathecal Morphine and Clonidine in the Treatment of Pain After Spinal Cord Injury

Abstract

We performed a double-blinded, randomized, controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine, alone or combined, in the treatment of neuropathic pain after spinal cord injury. The combination of morphine and clonidine produced significantly more pain relief than placebo 4 h after administration; either morphine or clonidine alone did not produce as much pain relief. In addition, lumbar and cervical cerebrospinal fluid (CSF) concentrations, sampled at these levels at different times after administration were examined for a relationship between pain relief and CSF drug concentration. Lumbar CSF drug concentrations were initially several orders of magnitude larger than those in cervical CSF. After 1-2 h, the concentrations of morphine in cervical CSF markedly exceeded those of clonidine. The concentration of morphine in the cervical CSF and the degree of pain relief correlated significantly. We conclude that intrathecal administration of a mixture of clonidine and morphine is more effective than either drug administered alone and is related to the CSF-borne drug concentration above the level of spinal cord injury. If there is pathology that may restrict CSF flow, consideration should be given to intrathecal administration above the level of spinal cord damage to provide an adequate drug concentration in this region.

Successful reduction of neuropathic pain associated with spinal cord injury via of a combination of intrathecal hydromorphone and ziconotide: a case report

“…The relative opiate sensitivity/resistance of various types of SCI-associated neuropathic pain (ie above-level, at-level and below-level) is unknown. In the study performed by Siddall et al, 17 there was a suggestion of a differential responsive to at-level and below-level pain components. In the patient described in this case report, specific responses to intrathecal medications were observed.…”

A Systematic Review of Pharmacologic Treatments of Pain After Spinal Cord Injury

“…Two studies 62,63 have demonstrated the synergistic effects of intrathecal morphine and clonidine. Their findings suggest that different subtypes of neuropathic pain may respond differently to pharmacological interventions; pain localized to the level of the SCI may be more susceptible to drugs directed at the spinal level, while pain below the level of the SCI may be associated with changes at the thalamic (central) level.…”

“…Their findings suggest that different subtypes of neuropathic pain may respond differently to pharmacological interventions; pain localized to the level of the SCI may be more susceptible to drugs directed at the spinal level, while pain below the level of the SCI may be associated with changes at the thalamic (central) level. 62 Accordingly, deafferent and dysaesthetic neuropathic pain may also respond differently to specific treatments although there are challenges in distinguishing between the two; moreover, most studies did not specify the type of neuropathic pain and hence effectively evaluating treatments was not possible.…”

“…Siddall et al 62 conducted an RCT/cross-over trial of intrathecal morphine, clonidine or placebo given at the lumbar level in 20 subjects with post-SCI neuropathic pain. Once a subject achieved satisfactory pain relief or suffered drug side effects with one of the three treatments, that subject was treated with a mixture of clonidine and morphine.…”

“…Both morphine and clonidine given alone demonstrated a trend towards pain reduction; however, when the combination of morphine and clonidine was administered, there was a significant reduction in pain. Siddall et al 62 postulated that administering half the effective minimum dose of clonidine and morphine together resulted in a synergistic benefit and reduction in pain.…”