Figure 6

Sensitization of capsaicin responses after acute (A) and chronic (B) oxaliplatin treatment; Sensitization of responses to icilin (C), but not WS12 (D), after oxaliplatin treatment. A. Graph showing the average magnitude of desensitization (2^nd bar) normalised to the first response (1^st bar) in vehicle treated neurons. Acute oxaliplatin treatment resulted in significantly enhanced second responses (3^rd bar), compared to the first capsaicin response, that was reversed by preincubation with 5 μM CB2 agonist GW833972 (4^th bar). B. Chronic treatment with oxaliplatin for 48 hours also enhanced responses to 200 nM capsaicin (n.s. at 5 μg/ml oxaliplatin, but highly significant at 20 and 50 μg/ml oxaliplatin). C. Vehicle treated neurons responded to 1 μM icilin with calcium influx (1^st bar), and a smaller second response following washout (2^nd bar). Pretreatment with 20 μg/ml oxaliplatin before the second icilin stimulus significantly enhanced responses to 1 μM icilin (3^rd bar), and significantly higher than the second icilin response without oxaliplatin (P = 0.005). Similarly, chronic oxaliplatin treatment (20 μg/ml for 24 hours), also resulted in significantly enhanced second responses to 1 μM icilin compared to those without oxaliplatin (P < 0.05). D. Vehicle treated neurons responded to the TRPM8 specific ligand WS-12 (20 μM stimulus), with calcium influx (1^st bar). Following washout, a second 20 μM WS-12 stimulus resulted in a reduced response (2^nd bar), that was unaffected by the presence of oxaliplatin.