Molecular, Anatomical, Physiological, and Behavioral Studies of Rats Treated with Buprenorphine after Spinal Cord Injury

Abstract

Acute pain is a common symptom experienced after spinal cord injury (SCI). The presence of this pain calls for treatment with analgesics, such as buprenorphine. However, there are concerns that the drug may exert other effects besides alleviation of pain. Among those reported are in vitro changes in gene expression, apoptosis, and necrosis. In this investigation, the effect of buprenorphine was assessed at the molecular, behavioral, electrophysiological, and histological levels after SCI. Rats were injured at the T10 thoracic level using the NYU impactor device. Half of the animals received buprenorphine (0.05 mg=kg) for 3 consecutive days immediately after SCI, and the other half were untreated. Microarray analysis (n ¼ 5) was performed and analyzed using the Array Assist software. The genes under study were grouped in four categories according to function: regeneration, apoptosis, second messengers, and nociceptive related genes. Microarray analysis demonstrated no significant difference in gene expression between rats treated with buprenorphine and the control group at 2 and 4 days post-injury (DPI). Experiments performed to determine the effect of buprenorphine at the electrophysiological (tcMMEP), behavioral (BBB, grid walking and beam crossing), and histological (luxol staining) levels revealed no significant difference at 7 and 14 DPI in the return of nerve conduction, functional recovery, or white matter sparing between control and experimental groups ( p > 0.05, n ¼ 6). These results show that buprenorphine (0.05 mg=kg) can be used as part of the postoperative care to reduce pain after SCI without affecting behavioral, physiological, or anatomical parameters.

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: Their antioxidant effect and role of estrogen receptor alpha

“…A moderate contusion injury was induced using the NYU impactor device (Santiago et al, 2009) in at least five groups of animals containing: a) control-empty silastic implants, b) implants with 3 mg of estradiol, c) implants with 2 mg of MPP dihydrochloride (estrogen receptor α antagonist), d) silastic implants with estradiol and MPP, or e) 15 mg of TAM pellets. Briefly, the back of the animals were shaved and disinfected with iodine and alcohol.…”

Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats

“…All surgical procedures were performed as described previously. 23,24 Vaginal smears were performed on at least five animals from each group to determine the estrus cycle stage of the animals. Cytology evaluation was performed blinded to treatment at the moment of surgery and gave us a representation of the cycle of the complete population of animals used for this study.…”

“…25 Animals were sutured, and post-operative care included antibiotic injection (25 mg/kg cefazolin for 7 days), subcutaneous saline administration, eyedrops (to prevent excessive dryness to the cornea), and buprenorphine (Reckett & Colman Pharmaceuticals, Richmond, VA; 0.05 mg/kg) application twice a day for 3 days. 24 Bladders were manually voided three times a day until micturition reflexes were fully reestablished (5-7 days). All animals were housed individually after laminectomy or SCI.…”

“…The amount of white matter spared tissue was determined by staining transverse tissue sections with Luxol fast blue as reported previously. 15,24,31 To have a representation of the lesion epicenter, a total of three sections (*200 lm apart) were selected for each animal evaluated in the Luxol fast blue experiments. Photomicrographs were taken using Motic (version 1.2 software).…”

“…15,24,31 Representative images (10x) were captured with Nikon E20L inverted microscope with DSRI2 CMOS camera. Briefly, to determine the amount of white matter spared tissue per area, the stained section of the spinal cord was delineated, selected, and the density per area (D · A) measured.…”