Bee Venom and Pain

Involvement of Rac1 signalling pathway in the development and maintenance of acute inflammatory pain induced by bee venom injection

“…Taken together, it is possible that BV‐induced long‐term plastic changes of spinal WDR neurons may be caused by dendritic spine remodelling via activation of GTP‐Rac1‐PAK‐ERK/p38 MAPK signalling. This presumption can be supported by our previous results showing significant suppression of the BV‐induced spinal WDR neuronal spike discharges and enhancement of evoked responsiveness by cord dorsum application of ERK and p38 MAPK inhibitors (Yu and Chen, ; Li et al , ; see also Chen and Guan, ) and inhibition of the BV‐induced persistent spontaneous nociception and pain hypersensitivity by a p38 MAPK inhibitor (Cao et al , ). Whether dendritic spines of spinal dorsal horn neurons also undergo malformation and contribute to different behavioural phenotypes following s.c. BV injection warrants further studies.…”

“…Pre‐administration of intrathecal NSC23766 could also prevent the primary thermal and mechanical pain hypersensitivity (injection paw) as well as the mirror‐image thermal pain hypersensitivity (contralateral paw), in a dose‐dependent manner ( P < 0.05 Veh + BV vs. Control, n = 14–18 animals for each group; P < 0.05 NSC + BV vs. Veh + BV; n = 6–7 animals for each dose; Figure ). Because s.c. BV is known not to induce mirror‐image mechanical pain hypersensitivity (Chen and Chen, ; Chen and Lariviere, ; Chen and Guan, ), the failure to change the mechanical sensitivity of the contralateral paw by either of the three doses of intrathecal NSC23766 implied that activation of Rac1 signalling was not involved in the physiological process of pain sensation.…”

“…Our previous studies have shown that ERKs, p38 MAPK and JNK in the spinal dorsal horn can be phosphorylated by s.c. BV injection (Cui et al , ). Moreover, the spinal or peripheral inhibition of ERKs, p38 MAPK and JNK could differentially modulate BV‐induced or melittin‐induced pain‐related behaviours (Yu and Chen, ; Cao et al , ; Cui et al , ; Hao et al , ; Chen et al , ; see also Chen and Lariviere, ; Chen and Guan, ). Peripheral inhibition of ERK could suppress melittin‐induced long‐lasting spike discharges and enhancement of thermally nociceptive responsiveness of WDR neurons (Li et al , ; Yu et al , ).…”

“…The BV test is a well-established experimental pain model that can be used for studying the central and peripheral mechanisms underlying pathological pain (Chen, 2003(Chen, , 2007(Chen, , 2008Chen and Lariviere, 2010;Chen and Guan, In press). It has many advantages over other inflammatory pain models, which use stimuli such as formalin, carrageenan and zymosan, because of it resembles a natural injury and exhibits clinical symptoms that are similar to those experienced by many patients (Chen and Lariviere, 2010;Chen and Guan, 2015). The s.c. injection of BV into the rat hindpaw induces persistent spontaneous pain-related behaviours (for at least 1 h) and pain hypersensitivity (for 72-96 h) in a dose-dependent manner (Lariviere and Melzack, 1996;Chen et al, 1999b;Chen and Lariviere, 2010;Chen and Guan, 2015).…”

“…It has many advantages over other inflammatory pain models, which use stimuli such as formalin, carrageenan and zymosan, because of it resembles a natural injury and exhibits clinical symptoms that are similar to those experienced by many patients (Chen and Lariviere, 2010;Chen and Guan, 2015). The s.c. injection of BV into the rat hindpaw induces persistent spontaneous pain-related behaviours (for at least 1 h) and pain hypersensitivity (for 72-96 h) in a dose-dependent manner (Lariviere and Melzack, 1996;Chen et al, 1999b;Chen and Lariviere, 2010;Chen and Guan, 2015). The spontaneous pain-related behaviours consist of spinally organized flinch reflexes (You and Chen, 1999;You et al, 2003aYou et al, , 2003bYou et al, , 2003cLi and Chen, 2004;Chen and Lariviere, 2010) and supraspinally mediated licking and lifting behaviours on the side of the injected paw (Ren et al, 2008).…”