Articles: hyperalgesia.
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Arthritis and rheumatism · Mar 2011
A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor α-induced inflammatory hyperalgesia and Freund's complete adjuvant-induced monarthritis.
To investigate the involvement of transient receptor potential ankyrin 1 (TRPA1) in inflammatory hyperalgesia mediated by tumor necrosis factor α(TNFα) and joint inflammation. ⋯ Evidence suggests that endogenous activation of peripheral TRPA1 receptors plays a critical role in the development of TNFα-induced mechanical hyperalgesia and in sustaining the mechanical hyperalgesia observed after intraaarticular injection of CFA. These results suggest that blockade of TRPA1 receptors may be beneficial in reducing the chronic pain associated with arthritis.
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Diminished GABAergic and glycinergic inhibition in the spinal dorsal horn contributes significantly to chronic pain of different origins. Accordingly, pharmacological facilitation of GABAergic inhibition by spinal benzodiazepines (BDZs) has been shown to reverse pathological pain in animals as well as in human patients. Previous studies in GABA(A) receptor point-mutated mice have demonstrated that the spinal anti-hyperalgesic effect of classical BDZs is mainly mediated by GABA(A) receptors containing the α2 subunit (α2-GABA(A) receptors), while α1-GABA(A) receptors, which mediate the sedative effects, do not contribute. ⋯ When non-sedative doses of HZ166 and gabapentin, a drug widely used in the clinical management of neuropathic pain, were compared, the efficacies of both drugs against CCI-induced pain were similar. At doses producing already maximal antihyperalgesia, HZ166 was devoid of sedation and motor impairment, and showed no loss of analgesic activity during a 9-day chronic treatment period (i.e. no tolerance development). These findings provide further evidence that compounds selective for α2- and α3-GABA(A) receptors might constitute a novel class of analgesics suitable for the treatment of chronic pain.
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Peripheral ischemia is commonly associated with an increase in tissue ATP concentration and a decrease in tissue pH. Although in vitro data suggest that low tissue pH can affect ATP-binding affinities to P2 receptors, the mechanistic relationship between ATP and low pH on peripheral nociception has not been fully examined. This study was designed to investigate the potential role of an acidified environment on intraplantar αβmeATP-induced peripheral pain responses in rats. ⋯ Moreover, amiloride injection significantly reduced low pH-induced facilitation of αβmeATP-mediated MA, but not TH. These results demonstrate that low tissue pH facilitates ATP-mediated MA via the activation of P2X receptors and ASICs, whereas TH induced by ATP under low pH conditions is mediated by the P2Y1 receptor and TRPV1, but not ASIC. Thus distinct mechanisms are responsible for the development of MA and TH under conditions of tissue acidosis and increased ATP.
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J. Pharm. Pharmacol. · Mar 2011
Aβ and Aδ but not C-fibres are involved in stroke related pain and allodynia: an experimental study in mice.
Cerebral ischaemia is a leading cause of death and disability, including severe complications such as memory disturbance, palsy, and spasticity. Central post-stroke pain (CPSP) is a complication of cerebral ischaemia, and is characterized clinically by spontaneous pain and attacks of allodynia and dysaesthesia. However, the detailed mechanisms of CPSP are not well established. Herein, we have examined alterations of the current stimulus threshold of primary afferent neurons or the nociceptive threshold against mechanical stimuli in mice receiving left middle cerebral artery occlusion (MCAO). ⋯ The data suggested the development of bilateral hyperaesthesia in this model. Further, mechanical allodynia developed in the ipsilateral side to the MCAO. Potentially, myelinated A fibre-specific hypersensitization after stroke may have contributed to these symptoms.
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To compare the sensitivity of stimulating the plantar and dorsal hindpaw surfaces in the detection of mechanical allodynia and morphine analgesia. ⋯ Reliable and sensitive assessment of animal pain behaviors is critical to translational pain research. This study demonstrates the importance of using proper test protocols in animal studies and its implication in preclinical screening of potential analgesics.