An animal model of Burning Mouth Syndrome (BMS) for assessment of peripheral gamma-aminobutuyric acid A (GABAA) receptors as an analgesic target

• Main Author: Tan, Sun Nee
• Language: English
• Published: University of British Columbia 2013
• Online Access: http://hdl.handle.net/2429/43890

Burning Mouth Syndrome (BMS) is a chronic pain syndrome characterised by burning pain in patients with clinically normal oral mucosa (Grushka et al., 2002). The prevalence of BMS increases with age and occurs far more commonly in women, with estimated female to male ratios ranging from 3:1 to 16:1 (Grushka, 1987b, van der Ploeg et al., 1987, Clark G.T, 2005). In women, there is a strong correlation between the development of BMS and the onset of menopause (Lipton et al., 1993, Bergdahl and Bergdahl, 1999). A proposed theory is that deprivation of oestrogen produces atrophic changes within the oral epithelium (Valimaa et al., 2004) leading to symptoms of BMS. Therefore, I employed immunohistochemistry and electrophysiology techniques to test the hypotheses that ovariectomised rats will show reduced nerve fibre densities and lower proportions of peptidergic neuronal fibres (small-diameter fibres) in the tongues leading to reduced thermal and mechanical thresholds of afferent fibres. A non-conventional treatment for BMS that seems effective (Gremeau-Richard et al., 2004) is sucking a tablet of the benzodiazepine (BZD), clonazepam, without swallowing. This treatment is speculated to decrease pain by activating peripheral ɣ-aminobutyric acid receptors A (GABAA) receptors in the oral cavity. Expression of GABAA receptors in tongue afferent fibres has yet to be demonstrated. Also, evidence for a direct effect of BZDs on nociceptors in the oral mucosa is lacking. My hypotheses are: GABAA receptors are present on both peptidergic and non-peptidergic nerve fibres. Activation of peripheral GABAA receptors will increase mechanical thresholds of tongue nerve fibres which would explain the therapeutic efficacy of topical clonazepam in human BMS. This study found high proportions of GABAAʏ²- containing, peptidergic (94%) and GABAAʏ²-containing, non-peptidergic (93%) tongueaxonal fibres of intact female rats. In intact females, muscimol and ɣ-aminobutyric acid (GABA) solutions had no effect on relative mechanical thresholds of afferent fibres. After thermal stimulation, muscimol significantly increased relative mechanical thresholds of afferent fibres. Ovariectomised and sham-operated rats did not differ in any of the parameters measured. Topical applications of muscimol and bicuculline solutions did not have any significant effect on relative mechanical thresholds of nerve fibres in both rat groups.