Mechanical hyperalgesia

Davis A, Perkins M The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat. Br J Pharmacol 1994 113 63-68. 

Zahn, P. K. and Brennan, T. J. Intrathecal metabotropic glutamate receptor antagonists do not decrease mechanical hyperalgesia in a rat model of postoperative pain, Anesth. Analg. 1998, 87, 1354-1359. 

L-701,324 has been shown to reverse the inflammation-induced mechanical hyperalgesia in rats without affecting the accompanying carrageenan-induced paw edema (Laird et al., 1996). 

Both remacemide and its des-glycinyl-metabolite inhibit the inflammatory, mechanical hyperalgesia as well as the edema induced by injection of carrageenan or complete Freunds adjuvant into the rat hind paw (Asghar et al.,... 

Laird, J. M. A., Mason, G. S., Webb, J., Hill, R. G., Hargreaves, R. J. Effects of a partial agonist and a full antagonist acting at the glycine site of the NMDA receptor on inflammation-induced mechanical hyperalgesia in rats, Br. J. Pharmacol. 1996, 117, 1487-1492. 

Studies to elucidate the functional role of NO have used inhibitors of NO synthase such as L-NAME and L-NMMA (see below). Systemic and intrathecal injections of NO synthase inhibitors have been shown to reduce noxious responses to formalin and carrageenan-induced hyperalgesia (Sakurada et al., 2001). Furthermore, NO-induced mechanical hyperalgesia has been reported to be mediated by supraspinal centers and does not occur in in vitro preparations of the spinal cord. 

Pathirathna S, Todorovic SM, Covey DF et al. (2005) 5a-reduced neuroactive steroids alleviate thermal and mechanical hyperalgesia in rats with neuropathic pain. Pain 117 326-339... 

The analgesic effects of (+)-WIN55212-2 mesylate, an (aminoalkyl)indole derivative, in a rat model of neuropathic pain have been recorded [158]. The (-)-enantiomer was inactive. It was shown that a moderate dose (2.14 mg/ kg) completely alleviated the thermal and mechanical hyperalgesia, and mechanical allodynia without side-effects. The results also suggested that changes in cannabinoid receptors occur in nerve injured animals. 

Simone DA, Baumann TK, LaMotte RH (1989) Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin. Pain 38 99-107... 

Inglis J J, Nissim A, Lees D M, et al. (2005). The differential contribntion of tnmour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation. Arthrit. Res. Ther. 7 R807-816. 

Malik-Hall M, Dina O A, Levine JD (2005). Primary afferent nociceptor mechanisms mediating NGF-indnced mechanical hyperalgesia. Euro. J. Neurosci. 21 3387-3394. 

TRPVl does not seem to be required for appropriate temperature sensing, as TRPVl-deficient mice show a normal phenotype for temperature detection (Davis et al. 2000). However, TRPVl is required to develop thermal hyperalgesia (Davis et al. 2000). Deletion of TRPVl resulted also in altered urinary bladder function (Birder et al. 2002). The possibility that TRPVl contributes also to mechanical hyperalgesia derives not from genetic studies (Davis et al. 2000), but from more recent pharmacological evidence obtained with first-generation (capsazepine)... 

Vergnolle N, Bunnett NW, Sharkey KA, et al. (2001) Proteinase-activated receptor-2 and hyperalgesia A novel pain pathway. Nat Med 7 821-826 Walker KM, Urban L, Medhurst SJ, et al. (2003) The VRl antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain. J Pharmacol Exp Ther... 

In a rat model of diabetic neiu-opathic pain, treatment with neramexane (12.3,24.6, and 49.2 mg/kg per day) for 2 weeks via an osmotic minipmnp significantly reduced symptoms of mechanical hyperalgesia and aUodynia. Administration of memantine (20 mg/kg per day) was comparable to gabapentin (50 mg/kg per day) [3]. 

In this maimer, capsaicin binds to the same group of nociceptors which lead to the sensation of pain, heat, and acid. Then lead for a reduction in pain and inflammation by depleting the neurotransmitter pain signaling [111]. This effect has been observed for example when an intraarticular injection of capsaicin is administrated to reduce the mechanical hyperalgesia induced in osteoarthritis [112]. Additionally, capsaicin appears to be effective in protecting bone from osteoarthritic damage, supporting the hypothesis that capsaicin-sensitive sensory neurons contribute to bone lesions. Therefore capsaicin may be useful for the development of new therapeutic approaches to pain control and prevention of osteoarthritis-dependent bone loss [113]. 

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