J Pain. 2015 Nov 18. pii: S1526-5900(15)00943-8
The chemotherapeutic agent, oxaliplatin produces a robust painful neuropathy resulting in the loss of intraepidermal nerve fibers (IENFs). We have previously reported that an acupoint injection of diluted bee venom (DBV) produces a temporary anti-allodynic effect in oxaliplatin-induced neuropathic mice. Here we show a significant long-lasting antinociceptive effect of repetitive DBV acupoint treatment on oxaliplatin-induced mechanical allodynia and a significant reduction in the loss of IENFs.
DBV (0.1mg/kg, s.c.) was administered once a day for 18 days beginning on day 15 after oxaliplatin injection. Immunohistochemistry for IENF was performed on the glabrous skin of the hind-paw foot pad using the pan-neuronal marker, protein gene product 9.5. A temporary increase in mechanical threshold was observed 60 min after a single DBV injection into the Zusanli acupoint, and this effect was enhanced over time by repetitive DBV treatments. The basal mechanical threshold prior to daily DBV injection also increased from day 7 post-DBV injections, and peaked at day 14 after DBV treatment. Moreover, the oxaliplatin-induced loss of IENFs was significantly reduced in repetitive DBV-treated mice.
Repetitive pretreatment with the alpha-2 adrenoceptor antagonist, yohimbine (5mg/kg, s.c.) completely prevented both the anti-allodynic effects and the increase in IENFs observed in repetitive DBV-treated mice.