Pain
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Comparative Study
Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia.
Although the N-arachidonoyl ethanolamine (anandamide) binds to cannabinoid receptors and has been implicated in the suppression of pain, its rapid catabolism in vivo by fatty acid amide hydrolase (FAAH) has presented a challenge in investigating the physiological functions of this endogenous cannabinoid. In order to test whether anandamide and other non-cannabinoid fatty amides modulate nociception, we compared FAAH (+/+) and (-/-) mice in the tail immersion, hot plate, and formalin tests, as well as for thermal hyperalgesia in the carrageenan and the chronic constriction injury (CCI) models. FAAH (-/-) mice exhibited a CB1 receptor-mediated phenotypic hypoalgesia in thermal nociceptive tests. ⋯ In contrast, no genotype differences in pain behavior were evident following CCI, which was instead found to obliterate the phenotypic hypoalgesia displayed by FAAH (-/-) mice in the tail immersion and hot plate tests, suggesting that nerve injury may promote adaptive changes in these animals. Collectively, these findings demonstrate a cannabinoid receptor-mediated analgesic phenotype in FAAH (-/-) mice. In more general terms, these findings suggest that selective inhibitors of FAAH might represent a viable pharmacological approach for the clinical treatment of pain disorders.
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Electronic diary assessment methods offer the potential to accurately characterize pain and other daily experiences. However, the frequent assessment of experiences over time often results in missing data. It is important to identify systematic reasons for missing data because such a pattern may bias study results and interpretations. ⋯ The most common self-reported reasons for missing interviews were failure to hear the computer alarm (49%) and inconvenient time (21%). Although there was some suggestion that persistent negative mood and stress were associated with missing electronic interviews in a subgroup of patients, on the whole, the patient demographic and clinical characteristics, treatment, and daily fluctuations in pain, activity interference, mood, and stress were not associated significantly with missing daily electronic interviews. The results provide further support for the use of electronic diary methodology in pain research.
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We examined congruence between chronic pain patients and their spouses on their reports of patient pain severity, patient disability, and spouse responses to pain. Patients reported that they were more physically and psychosocially disabled than their spouses reported them to be. However, spouses reported that the patients' pain was more severe than patients reported. ⋯ Male patient couples did not report differences on physical disability. Findings relating to other forms of disability and to spouse responses are also described. The results are discussed in the context of an interpersonal perspective of chronic pain and have implications for the assessment of pain and disability.
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We reported recently that redox agents, including the endogenous amino acid L-cysteine, modulate T-type Ca2+ currents in primary sensory neurons in vitro, and alter mechanical and thermal nociception in peripheral nociceptors in vivo in intact animals [Neuron 31 (2001) 75]. Here, we studied the effects of locally applied redox agents (L-cysteine and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) on thermal hyperalgesia in animals with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. We found that, following injection into the peripheral receptive fields, the endogenous reducing agent L-cysteine increased thermal hyperalgesia in a dose-dependent manner in rats with CCI of the sciatic nerve as well as in sham-operated rats. ⋯ Mibefradil, a potent and preferential T-type Ca2+ channel blocker, abolished L-cysteine-induced increase in thermal hyperalgesia in both animal groups suggesting the involvement of T-type Ca2+ channels in peripheral nociception. These results indicate for the first time that redox modulation of T-type Ca2+ channels in rat peripheral nociceptors is operational in pain states caused by peripheral axonal injury. Since thermal hyperalgesia is a common symptom of axonal injury, locally applied oxidizing agents could be used as a novel treatment to ameliorate neuropathic pain.