Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Gut pain and hyperalgesia induced by capsaicin: a human experimental model.
Human experimental visceral pain models using chemical stimulation are needed for the study of visceral hyperexcitability. Our aim was to stimulate the human gut with chemical activators (capsaicin, glycerol) and measure quantitatively the induced hyperexcitability to painful mechanical gut distension. Ten otherwise healthy subjects with an ileostoma participated. ⋯ No significant manifestations were found after application of glycerol and saline. Application of capsaicin to the human ileum induces pain and mechanical hyperalgesia. Specific activation of nociceptors in the gut mucosa provides new possibilities to study clinical relevant visceral pain mechanisms.
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Randomized Controlled Trial Clinical Trial
Injection of nerve growth factor into human masseter muscle evokes long-lasting mechanical allodynia and hyperalgesia.
Nerve growth factor (NGF) is a neurotrophic protein with a pivotal role in development and maintenance of the nervous system on one side and inflammatory and neuropathic pain states on the other. NGF causes clear signs of behavioral hyperalgesia in animal models and following intradermal and systemic administration in humans. The present double-blinded, placebo-controlled study was designed to test quantitatively the effect and duration (1h, 1, 7, 14, 21 and 28 days) of NGF (5 microg in 0.2 ml) injected into the masseter muscle. ⋯ Systemic adverse effects were noted in one subject who reported fever and slight discomfort about 8h after the NGF injection. In conclusion, this is the first study to show that injection of NGF into the human masseter muscle causes local signs of mechanical allodynia and hyperalgesia that persist for at least 7 days as well as pain during strenuous jaw movement. The present pain model is safe and may be used to gain further insight into the neurobiological mechanisms of muscle pain and sensitization.
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Using a model of visceral nociception, we examined whether cholecystokinin (CCK) acts as an anti-opioid peptide in the rat rostral ventromedial medulla (RVM). Because such interaction may be affected by inflammation, rats with and without inflamed colons were studied. The visceromotor response to noxious colorectal distension (CRD), quantified electromyographically, was recorded before and after intra-RVM administration of CCK, CCK receptor antagonists, and morphine. ⋯ Intra-RVM CCK-8 peptide enhanced responses to CRD in intracolonic vehicle-treated, but not TNBS-treated rats. Intra-RVM naloxone was without effect in intracolonic vehicle-or TNBS-treated rats, suggesting an absence of tonic opioid activity in RVM. These results document a CCK-opioid interaction in RVM, suggesting that colon inflammation leads to tonic activity at CCK(B) receptors in RVM.
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GABA and glycine are inhibitory neurotransmitters used by many neurons in the spinal dorsal horn, and intrathecal administration of GABA(A) and glycine receptor antagonists produces behavioural signs of allodynia, suggesting that these transmitters have an important role in spinal pain mechanisms. Several studies have described a substantial loss of GABA-immunoreactive neurons from the dorsal horn in nerve injury models, and it has been suggested that this may be associated with a loss of inhibition, which contributes to the behavioural signs of neuropathic pain. We have carried out a quantitative stereological analysis of the proportions of neurons in laminae I, II and III of the rat dorsal horn that show GABA- and/or glycine-immunoreactivity 2 weeks after nerve ligation in the chronic constriction injury (CCI) model, as well as in sham-operated and nai;ve animals. ⋯ However, we did not observe any change in the proportion of neurons in laminae I-III of the ipsilateral dorsal horn that showed GABA- or glycine-immunoreactivity compared to the contralateral side in these animals, and these proportions did not differ significantly from those seen in sham-operated or nai;ve animals. In addition, we did not see any evidence for alterations of GABA- or glycine-immunostaining in the neuropil of laminae I-III in the animals that had undergone CCI. Our results suggest that significant loss of GABAergic or glycinergic neurons is not necessary for the development of thermal hyperalgesia in the CCI model of neuropathic pain.
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J. Pharmacol. Exp. Ther. · Jul 2003
N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: II. in vivo characterization in rat models of inflammatory and neuropathic pain.
The vanilloid receptor 1 (VR1) is a cation channel expressed predominantly by nociceptive sensory neurons and is activated by a wide array of pain-producing stimuli, including capsaicin, noxious heat, and low pH. Although the behavioral effects of injected capsaicin and the VR1 antagonist capsazepine have indicated a potential role for VR1 in the generation and maintenance of persistent pain states, species differences in the molecular pharmacology of VR1 and a limited number of selective ligands have made VR1 difficult to study in vivo. N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropryazine-1(2H)-carbox-amide (BCTC) is a recently described inhibitor of capsaicin- and acid-mediated currents at rat VR1. ⋯ BCTC also reduced mechanical hyperalgesia and tactile allodynia 2 weeks after partial sciatic nerve injury (10 and 30 mg/kg p.o.). BCTC did not affect motor performance on the rotarod after administration of doses up to 50 mg/kg p.o. These data suggest a role for VR1 in persistent and chronic pain arising from inflammation or nerve injury.