buprenorphine and Facial-Pain

The injection of low dose buprenorphine to the sympathetic ganglia, termed "GLOA", Ganglionide Local Opioid Analgesia, is used to treat chronic pain in several European centres. It is not known whether the clinically observed GLOA effect in chronic pain syndromes is due to a specific effect of buprenorphine at the ganglia. We assessed whether GLOA, plus intramuscular saline, was more efficacious than the reverse, saline injection to the stellate plus intramuscular buprenorphine, termed SSB.. We devised a randomized, double-blinded, controlled crossover trial to treat patients with chronic upper body pain syndromes. Patients first received either GLOA or SSB. Pain was assessed using pain diaries both before injection and over the first 8h and 6days afterwards, and was expressed as relative pain intensity post versus pre-injection pain.. The median relative pain intensity after injections did not differ between GLOA and SSB. Four patients reported a low, <50%, relative pain level over the first 8h after SSB only. Four patients did not complete the trial and were excluded. One patient with cardiomyopathy became acutely diaphoretic and fatigued after GLOA, his vital signs however remained stable.. We failed to show a superiority of GLOA over SSB. Our results suggest it unlikely that the clinically observed effect after a single GLOA injection is due to a specific action of buprenorphine at the stellate ganglion. The efficacy of GLOA is hereby questioned. The use of GLOA in patients with cardiomyopathy should be cautioned.. ISRCTN59287260; http://www.controlled-trials.com/

Topics: Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Autonomic Nerve Block; Buprenorphine; Chronic Disease; Cross-Over Studies; Double-Blind Method; Facial Pain; Female; Humans; Injections; Injections, Intramuscular; Male; Middle Aged; Neck Pain; Pain Measurement; Shoulder Pain; Stellate Ganglion; Sympathetic Fibers, Postganglionic

Complete Freund's adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate post-induction phase. Few attempts have been made to counteract these adverse effects with analgesics. The present study investigated the effect of buprenorphine on animal welfare, pain-related behaviour and model-specific parameters during the disease progression in a rat model of CFA-induced monoarthritis. The aim was to reduce or eliminate unnecessary pain in this model, in order to improve animal welfare and to avoid suffering, without compromising the quality of the model. Twenty-four male Sprague Dawley rats were injected with 20 μl of CFA into the left tibio-tarsal joint to induce monoarthritis. Rats were treated with either buprenorphine or carprofen for 15 days during the disease development, and were compared to a saline-treated CFA-injected group or a negative control group. Measurements of welfare, pain-related behaviour and clinical model-specific parameters were collected. The study was terminated after 3 weeks, ending with a histopathologic analysis. Regardless of treatment, CFA-injected rats displayed mechanical hyperalgesia and developed severe histopathological changes associated with arthritis. However, no severe effects on general welfare were found at any time. Buprenorphine treatment reduced facial pain expression scores, improved mobility, stance and lameness scores and it did not supress the CFA-induced ankle swelling, contrary to carprofen. Although buprenorphine failed to demonstrate a robust analgesic effect on the mechanical hyperalgesia in this study, it did not interfere with the development of the intended pathology.

Topics: Analgesics, Opioid; Animals; Ankle Joint; Arthritis, Experimental; Behavior, Animal; Body Weight; Buprenorphine; Carbazoles; Corticosterone; Disease Models, Animal; Facial Pain; Freund's Adjuvant; Hyperalgesia; Male; Rats; Rats, Sprague-Dawley

A model system capable of providing clinically relevant analgesic doses with minimal trauma has been elusive in laboratory animal medicine. Our laboratory has developed an orofacial operant pain system that effectively discriminates between non-noxious and noxious thermal stimuli in rats and mice. Male and female rats (Crl:SD) and mice (Crl:SKR-HR(hr)) were trained to perform a task (placing their face through an opening and having their cheeks stay in contact with thermodes) to receive a reward (a solution of sweetened condensed milk). Currently accepted doses of buprenorphine were tested by using a crossover design. Pain was induced in both species by sensitizing the depilated skin over both cheeks with capsaicin cream or by creating a surgical incision (rats only) and then allowing the animals to contact a temperature-regulated thermode while obtaining a reward. Optimal antinociceptive doses included 0.05 and 0.1 mg/kg in male mice but only 0.05 mg/kg in female mice. In rats, optimal antinociceptive doses included 0.03 and 0.05 mg/kg for male rats but only 0.03 mg/kg for female rats. The 2 pain-induction models in rats (capsaicin cream and surgical incision) did not differ. Our orofacial operant pain assay can determine clinically relevant analgesic doses for rodents in a preclinical assay. The automated, investigator-independent nature of the assay, in conjunction with its high sensitivity, makes this method an improvement over traditional noninvasive methods, providing better data for developing optimal analgesic recommendations for rats and mice.

Topics: Analgesics; Analgesics, Opioid; Animals; Animals, Laboratory; Buprenorphine; Conditioning, Operant; Facial Pain; Female; Male; Mice; Pain Measurement; Rats; Rats, Sprague-Dawley; Reward; Rodent Diseases

To test the reliability and validity of a novel rat-holding device designed to be used in conjunction with the plantar test apparatus for studying nocifensive behavioral responses in an established model of temporomandibular joint (TMJ) pathology.. Thirty-five young adult male Sprague-Dawley rats were used. Withdrawal latencies in response to infrared 40 heat stimulation of the submandibular region in naïve animals (n = 4) and animals injected with saline or complete Freund's adjuvant (CFA) in the TMJ (n > 9) were measured over a 2-week time period. Nocifensive responses to mechanical stimulation of the cutaneous tissue directly over the TMJ with von Frey filaments were investigated in animals injected with CFA in the TMJ (n = 6). The effect on nocifensive responses to heat and mechanical stimulation of subcutaneous administration of buprenorphine (0.05 mg/kg) into the hindquarter was assessed in CFA and cotreated animals (n = 6). Statistical analysis was performed using a nonparametric Mann-Whitney U test.. Under basal conditions, withdrawal latencies to heat stimulation of the orofacial region remained consistently around 15 seconds over 14 days. Unilateral CFA injection in the TMJ significantly decreased heat-withdrawal latencies on days 1, 2, 7, and 14 in the ipsilateral side (P < .05), but not contralateral side, when compared with basal values. CFA also significantly decreased the nocifensive threshold to mechanical stimulation on days 1, 2, and 7 postinjection (P < .05). CFA-mediated changes in heat withdrawal and mechanical thresholds in the orofacial region were significantly suppressed by subcutaneous administration of buprenorphine into the hindquarter (P < .05).. Findings from this study provide evidence to validate the use of this holding device for studying nocifensive behaviors in the orofacial region of rats in response to heat or mechanical orofacial stimulation.

Topics: Analgesics, Opioid; Animals; Avoidance Learning; Behavior, Animal; Buprenorphine; Facial Pain; Freund's Adjuvant; Head Movements; Hot Temperature; Inflammation; Male; Neck; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reaction Time; Restraint, Physical; Temporomandibular Joint; Trigeminal Nerve

Combination of two or more analgesics is widely used for the treatment of moderate and severe pain syndromes, allowing usage of lower doses of each compound and thereby limiting side effects; there is currently a large interest in investigating the potential advantages of combinations between opioids and non-steroidal inflammatory drugs (NSAIDs), coxibs in particular. The rat orofacial formalin test is a useful pre-clinical model of inflammatory trigeminal pain for evaluating antinociceptive activity of analgesics and their combinations. Injection of formalin in the rat wiskerpad induces a stereotyped response (rubbing), consisting of two distinct phases: a first 'phasic' phase and a second 'tonic' phase. In this work we tested a partial agonist to mu-opioid receptors, buprenorphine, and a selective cyclo-oxygenase-2 inhibitor, lumiracoxib, each of which given i.p. either alone or in combination. Buprenorphine reduced nociception both in the first and in the second phase, whereas lumiracoxib induced antinociception in the second phase only. The interaction between the two drugs was assessed through isobolographic analysis after combined administration at a fixed dose ratio. Such combination produced a dose-dependent antinociceptive effect in both phases. We observed a statistical difference between the theoretical and the experimental ED(50), which indicated synergistic interaction in the second phase. Concerning the first phase, we assumed that the antinociceptive effects were almost completely to be attributed to buprenorphine, since lumiracoxib was ineffective when administered alone. However, we found an unexpected difference between the theoretical and experimental ED(50), suggesting synergism in the first phase as well.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Cyclooxygenase 2 Inhibitors; Diclofenac; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Facial Pain; Injections, Intraperitoneal; Male; Pain Measurement; Rats; Rats, Wistar; Receptors, Opioid, mu