Articles: hyperalgesia.
-
Anesthesia and analgesia · Sep 2006
Clinical TrialThe effect of intravenous ketorolac on capsaicin-induced deep tissue hyperalgesia.
Preclinical and clinical studies have emphasized that persistent small afferent input will induce a state of central facilitation that can be attenuated by systemically administered nonsteroidal antiinflammatory drugs. However, these studies have been performed using cutaneous models of hyperalgesia. In this study we evaluated the effects of IV ketorolac on an experimental model of deep tissue hyperalgesia using IM capsaicin. ⋯ The IM injection of capsaicin resulted in a reliable report of pain, hyperalgesia, and referred pain. Ketorolac had no effect on spontaneous pain, elicited pain, pain distribution, or secondary hyperalgesia induced by capsaicin. The findings of this study support the feasibility of further pharmacological studies using the IM capsaicin pain model.
-
Neuroscience research · Sep 2006
Assessing mechanical sensitivity of masseter muscle in lightly anesthetized rats: a model for craniofacial muscle hyperalgesia.
In this report, we present a simple and reliable way of assessing mechanical sensitivity of masseter muscle as a model for craniofacial muscle hyperalgesia. Mechanical thresholds that evoke nocifensive hindpaw responses following noxious masseter stimulation were assessed. ⋯ This lightly anesthetized rodent paradigm allows us to provide calibrated and reliable mechanical stimulus, which is not possible in behaving animals. The technique can be applied to study mechanistic bases for craniofacial muscle tenderness.
-
We investigated effects of topical application of ketanserin, a 5-HT2A receptor antagonist, on hyperalgesia and edema in the arthritic rat, a chronic pain model with inflammation. Unilateral, but not bilateral, arthritis was induced with intra-articular injection of a mixture of kaolin and carrageenan in one side, as indicated by the shortened paw withdrawal latency and an increase in the circumference of the knee joint. Topical application of ketanserin onto skin over the arthritic joint delivered in a mixture of gelatin, glycerol and kaolin produced dose-dependent attenuation of nociceptive and inflammatory effects resulting from intra-articularly injected kaolin/carrageenan. ⋯ In contrast, 3% ketanserin applied to skin of the knee joint on the non-inflamed side for 2 weeks did not alter nociceptive thresholds of the paw and the size of the knee joint in both the inflamed and non-inflamed limbs. These results indicate that 5-HT2A receptors in the periphery play a significant role in the maintenance and/or development of inflammatory pain. The present study suggests that topical ketanserin is a promising direction for potential clinical exploration to relieve established hyperalgesia and inflammation in arthritis without adverse effects and tolerance.
-
Hypersensitivity to mechanical stimulation is a well documented symptom of neuropathic pain, for which there is currently no effective therapy. Src-family kinases (SFKs) are involved in proliferation and differentiation and in neuronal plasticity, including long-term potentiation, learning, and memory. Here we show that activation of SFKs induced in spinal cord microglia is crucial for mechanical hypersensitivity after peripheral nerve injury. ⋯ In contrast, there was no change in SFK phosphorylation in primary sensory neurons, and PP2 did not decrease the induction of transient receptor potential ion channel TRPV1 and TRPA1 in sensory neurons. Together, these results demonstrate that SFK activation in spinal microglia contributes to the development of mechanical hypersensitivity through the ERK pathway. Therefore, preventing the activation of the Src/ERK signaling cascade in microglia might provide a fruitful strategy for treating neuropathic pain.