Oral buprenorphine is anti-inflammatory and modulates the pathogenesis of streptococcal cell wall polymer-induced arthritis in the Lew/SSN rat

Abstract

This study was carried out to determine an effective regimen for pain management in streptococcal cell wall (SCW)-induced arthritis in female Lew/SSN rats. Forty weanling rats lin 2 groups) were trained to accept disks of jelly as part of their dietary regimen. At 8 weeks of age weighing 150 g, SCW arthritis was induced and sublingual buprenorphine tablets were incorporated into the jelly disks to alleviate the pain of acute arthritis, which developed 24 h post-induction. Group A rats received buprenorphine at a rate of 1 mg/kg 12 hourly. Group B rats received buprenorphine at a rate of 2 mg/kg 12 hourly. Both groups of rats were monitored for symptoms of distress using an adaptation of the Morton and Griffin scale of adverse reactions. Group A rats with severe arthritis required additional subcutaneous (s.c.) injections of buprenorphine to alleviate the adverse effects of arthritis. Group B rats, with twice the dose of buprenorphine did not require additional s.c. injections of buprenorphine. Histological sections of rat hocks indicated that the inflammation was suppressed in Group B rats. We concluded that oral administration of buprenorphine is an effective method of pain management in the pathogenesis of SCW-induced arthritis in Lew/SSN rats. In this model of arthritis, oral buprenorphine has a significant anti-inflammatory effect and appears to modulate the destructive arthritic phase in joints in this animal model of arthritis.

Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis

“…For example, Hall et al showed that buprenorphine inhibits osteoclastic bone resorption in an adjuvant-induced arthritis rat model [16]. Oral administration of buprenorphine was also shown to modulate the disease pathogenesis of streptococcal cell wall polymer-induced arthritis in Lew/SSN rat [9]. Bas et al demonstrated the alleviation of mechanical hypersensitivity in buprenorphine-administered QB mice during the inflammatory and postinflammatory phases of arthritis [7].…”

“…For example, mitigation of arthritis-associated mechanical hypersensitivity was demonstrated in a study that administered buprenorphine at a dose of 0.1 mg/kg body weight [7]. Similarly, buprenorphine administrated at a high dose of 2 mg/kg in Lew/SSN rats showed anti-inflammatory effects and pathophysiological changes in a streptococcal cell wall polymer-induced arthritis [9]. Our findings clearly demonstrate that buprenorphine even at lower doses, and at a time point when there are no observed clinical symptoms, interferes in the expression of inflammatory and oxidative stress molecular markers in a murine model of CIA.…”

“…The CIA model is the most extensively used preclinical animal model of RA, as it elicits autoimmunity to collagen type II (CII), inflammation of synovial joints, cartilage destruction, and bone erosion [7, 8]. Several studies have demonstrated the anti-inflammatory effects of buprenorphine on rat models of various inflammatory diseases, including those in an adjuvant-induced arthritis model [9]. In this study, we showed that administration of buprenorphine as an analgesic altered the expression of specific molecular markers of inflammation and those related to oxidative stress response in a murine model of CIA.…”

Inosine Augments the Effects of a Nogo Receptor Blocker and of Environmental Enrichment to Restore Skilled Forelimb Use after Stroke

“…Other research in the field would suggest that the functional improvements commonly involve the use of compensatory strategies rather than recovery of the normal pattern of paw use (Whishaw et al, 1991). An additional point is that buprenorphine, which was used throughout as an analgesic, has anti-inflammatory effects (Volker et al, 2000) that may affect axonal sprouting in positive or negative ways (Yin et al, 2003; Steinmetz et al, 2005; Gensel et al, 2009; Stirling et al, 2009) and alter patterns of gene expression in the microarray studies.…”

The safety, efficacy and neuromotor effects of the neurosteroid anaesthetic alfaxalone in rats

“…Bupenorphine can be administered subcutaneously or orally in rats and mice (Liles and Flecknell, 1992a, Volker et al, 2000, Abelson et al, 2012 and has shown to be effective in treating multiple pain conditions including neuropathic pain (Guarnieri et al, 2012). Preanaesthetic subcutaneous (SC) administration of buprenorphine, during ketamine-medetomidine injectable anaesthesia, was associated with respiratory arrest and mortality in rats (Hedenqvist et al, 2000).…”