Natural products have been revealed as relevant sources of therapeutic agents including those for the management of
pain states. In this study, the anti-nociceptive and anti-inflammatory effects of (-)-
cassine, isolated from Senna spectabilis were evaluated using pharmacological, behavioural and biochemical approaches. Oral treatment with (-)-
cassine (3-30 mg/kg) reduced
carrageenan-induced mechanical and thermal nociception associated with the suppression of
myeloperoxidase activity in the mouse paw. Moreover, (-)-
cassine (1-10 μg/site) prevented
mechanical hyperalgesia induced by
carrageenan when given through the intraplantar (i.pl.), spinal and intracerebroventricular routes. Additionally, oral treatment with (-)-
cassine (3-60 mg/kg) prevented the
mechanical hyperalgesia elicited by intraplantar injection of
prostaglandin E(2), complete
Freund's adjuvant, interleukin-1β,
interleukin-6 and keratinocyte-derived
chemokine. Furthermore, (-)-
cassine inhibited the mechanical nociceptive response induced by
ligation of the sciatic nerve and also significantly reduced the levels of
cytokines/
chemokines in paw tissue following i.pl. injection of
carrageenan. In addition, the anti-nociceptive and anti-inflammatory actions of (-)-
cassine were associated with its ability to interact with both TRPV1 and TRPA1 receptors and by inhibiting the upregulation of cyclooxigenase-2 as well as inhibiting the phosphorylation of MAPK/ERK and the
transcription factor NF-κB. It is important to highlight that oral treatment with (-)-
cassine did not produce any effects related to temperature, locomotor activity or
catalepsy. Altogether, the present data demonstrate that (-)-
cassine has systemic, spinal and supraspinal anti-nociceptive properties when assessed in inflammatory and
neuropathic pain models. These effects are associated with its ability to block several signalling pathways associated with inflammatory and nociceptive responses. This article is part of a Special Issue entitled '
Post-Traumatic Stress Disorder'.