Summary: | 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.
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