Nociception and Pain

Context: Paeonia mascula is used in traditional medicine in North of Algeria for its anti-inflammatory activity. Aims: To evaluate the analgesic and the anti-inflammatory effects of the ethanolic extract of Paeonia mascula (EPM) in mice. Methods: The analgesic activity of EPM was evaluated on the chemical nociception in the animal models of acetic acid-induced writhing and formalin-induced hind paw licking/biting, whereas xylene-induced ear edema and multiapplication of TPA (12-O-tetradecanoylphorbol-13-acetate) were used to determine anti-inflammatory effects of EPM. Results: EPM (100 and 250 mg/kg) produced a significant dose-dependent inhibition of pain-related behaviors elicited by acetic acid. Also, EPM reduced both early and late phases of the formalin test. However, its inhibitory effect was more significant on tonic inflammatory phase, may be related to the anti-inflammatory abilities of this extract. Also, EPM decreased ear edema in acute and sub-chronic models used in the present study. Conclusions: These findings suggest the ethanolic extract from aerial parts of Paeonia mascula presents significant anti-inflammatory and anti-nociceptive effects on chemical behavioral models of nociception and inflammation in mice.

About 50 million of the U.S. adult population suffer from chronic pain. It is a complex disease in its own right for which currently available analgesics have been deemed woefully inadequate since ∼20% of the sufferers derive no benefit. Vitamin D, known for its role in calcium homeostasis and bone metabolism, is thought to be of clinical benefit in treating chronic pain without the side-effects of currently available analgesics. A strong correlation between hypovitaminosis D and incidence of bone pain is known. However, the potential underlying mechanisms by which vitamin D might exert its analgesic effects are poorly understood. In this review, we discuss pathways involved in pain sensing and processing primarily at the level of dorsal root ganglion (DRG) neurons and the potential interplay between vitamin D, its receptor (VDR) and known specific pain signaling pathways including nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), epidermal growth factor receptor (EGFR), and opioid receptors. We also discuss how vitamin D/VDR might influence immune cells and pain sensitization as well as review the increasingly important topic of vitamin D toxicity. Further in vitro and in vivo experimental studies will be required to study these potential interactions specifically in pain models. Such studies could highlight the potential usefulness of vitamin D either alone or in combination with existing analgesics to better treat chronic pain.

The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effect of mangiferin (MG); as well as its potential beneficial interactions with some standard analgesic drugs and sympathetic-mediated vasoconstriction and vasodilator agents during the earlier stage of the pathology. A single dose of MG (50 and 100 mg/kg, p.o.) decreased mechanical allodynia 72 h post-ischemia-reperfusion (I/R). MG 100 mg/kg, i.p. (pre- vs. post-drug) increased von Frey thresholds in a yohimbine and naloxone-sensitive manner. Sub-effective doses of morphine, amitriptyline, prazosin, clonidine and a NO donor, SIN-1, in the presence of MG were found to be significantly anti-allodynic. A long-term anti-allodynic effect at 7 and 13 days post-I/R after repeated oral doses of MG (50 and 100 mg/kg) was also observed. Further, MG decreased spinal and muscle interleukin-1β concentration and restored muscle redox status. These results indicate that MG has a transient and long-term anti-allodynic effect in CPIP rats that appears to be at least partially attributable to the opioid and α2 adrenergic receptors. Additionally, its anti-inflammatory and antioxidant mechanisms could also be implicated in this effect. The association of MG with sub-effective doses of these drugs enhances the anti-allodynic effect; however, an isobolographic analysis should be performed to define a functional interaction between them. These findings suggest the possible clinical use of MG in the treatment of CRPS-I in both early sympathetically maintained pain and long-term sympathetically independent pain.