Intrathecal Morphine Attenuates Recovery of Function after a Spinal Cord Injury

• Published in: Journal of neurotrauma Vol. 26; no. 5; pp. 741 - 752
• Main Authors: Hook, Michelle A., Moreno, Georgina, Woller, Sarah, Puga, Denise, Hoy, Kevin, Balden, Robyn, Grau, James W.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.05.2009
• Subjects: Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Animals; Autophagy - drug effects; Care and treatment; Clinical outcomes; Contusions - physiopathology; Diagnosis; Dose-Response Relationship, Drug; Drug delivery systems; Drug dosages; Drug therapy; Health aspects; Locomotion - physiology; Male; Morphine; Morphine - administration & dosage; Morphine - adverse effects; Morphine - therapeutic use; Muscle Spasticity - etiology; Muscle Spasticity - physiopathology; Narcotics; Pain; Pain - drug therapy; Pain - etiology; Pain management; Pain Measurement - drug effects; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Risk factors; Sensation - physiology; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - mortality; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Urinary Bladder Diseases - etiology; Urinary Bladder Diseases - physiopathology; Weight Gain - drug effects; United States
• ISSN: 0897-7151; 1557-9042; 1557-9042
• DOI: 10.1089/neu.2008.0710

Prior work has shown that a high dose (20 mg/kg) of systemic morphine, required to produce significant analgesia in the acute phase of a contusion injury, undermines the long-term health of treated subjects and increases lesion size. Moreover, a single dose of systemic morphine in the early stage of injury (24 h post-injury) led to symptoms of neuropathic pain 3 weeks later, in the chronic phase. The present study examines the locus of the effects using intrathecal morphine administration. Subjects were treated with one of three doses (0, 30, or 90 microg) of intrathecal morphine 24 h after a moderate contusion injury. The 90-microg dose produced significant analgesia when subjects were exposed to noxious stimuli (thermal and incremented shock) below the level of injury. Yet, despite analgesic efficacy, intrathecal morphine significantly attenuated the recovery of locomotor function and increased lesion size rostral to the injury site. A single dose of 30 or 90 microg of intrathecal morphine also decreased weight gain, and more than doubled the incidence of mortality and autophagia when compared to vehicle-treated controls. Morphine is one of the most effective pharmacological agents for the treatment of neuropathic pain and, therefore, is indispensable for the spinally injured. Treatment can, however, adversely affect the recovery process. A morphine-induced attenuation of recovery may result from increases in immune cell activation and, subsequently, pro-inflammatory cytokine concentrations in the contused spinal cord.