Articles: hyperalgesia.
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Clinical Trial
Influence of repeated painful procedures and sucrose analgesia on the development of hyperalgesia in newborn infants.
This study determined the effects of cumulative exposure to painful needle procedures and sucrose analgesia on the development of remote hyperalgesia in newborn infants, defined as an increase in response to a normally painful stimulus at a site distal from the site of injury. One-hundred and twenty healthy newborns and 120 healthy newborn infants of diabetic mothers equally randomized to sucrose analgesia or placebo prior to all needle procedures in the first two days after birth were divided into two exposure groups according to number of needle procedures they had undergone [high (> or =5) or low (< or =4)] using the median cut-off technique. Compared to the low exposure group, infants in the high exposure group had a higher pain response during a subsequent venipuncture distal to the site of previous injury, assessed by the Premature Infant Pain Profile (PIPP) [7.1 vs. 8.4; p=0.012] and Visual Analog Scale (VAS) [2.5 cm vs. 3.2 cm; p=0.047], and a trend for longer cry duration [25.7 s vs. 33.8 s; p=0.171]. ⋯ Sucrose reduced PIPP, VAS, and cry duration scores during venipuncture, but did not prevent hyperalgesia (p>0.05). There was a preponderance of infants of diabetic mothers in the high exposure group; however, the analysis did not demonstrate this to be a confounding factor. In conclusion, sucrose analgesia for repeated painful procedures in the first day of life does not prevent development of remote hyperalgesia in newborns.
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In animal studies, thermal sensitivity is mostly evaluated on the basis of nociceptive reaction latencies in response to a given thermal aversive stimulus. However, these techniques may be inappropriate to differentiate allodynia from hyperalgesia or to provide information differentiating the activation of nociceptor subtypes. The recent development of dynamic hot and cold plates, allowing computer-controlled ramps of temperature, may be useful for such measures. In this study, we characterized their interest for studying thermal nociception in freely moving mice and rats. We showed that escape behavior (jumps) was the most appropriate parameter in C57Bl/6J mice, whereas nociceptive response was estimated by using the sum of paw lickings and withdrawals in Sprague-Dawley rats. We then demonstrated that this procedure allows the detection of both thermal allodynia and hyperalgesia after peripheral pain sensitization with capsaicin in mice and in rats. In a condition of carrageenan-induced paw inflammation, we observed the previously described thermal hyperalgesia, but we also revealed that rats exhibit a clear thermal allodynia to a cold or a hot stimulus. These results demonstrate the interest of the dynamic hot and cold plate to study thermal nociception, and more particularly to study both thermal allodynia and hyperalgesia within a single paradigm in awake and freely moving rodents. ⋯ Despite its clinical relevance, thermal allodynia is rarely studied by researchers working on animal models. As shown after stimulation of capsaicin-sensitive fibers or during inflammatory pain, the dynamic hot and cold plate validated in the present study provides a useful tool to distinguish between thermal allodynia and thermal hyperalgesia in rodents.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Jul 2009
TRPA1 in mast cell activation-induced long-lasting mechanical hypersensitivity of vagal afferent C-fibers in guinea pig esophagus.
Sensitization of esophageal sensory afferents by inflammatory mediators plays an important role in esophageal nociception. We have shown esophageal mast cell activation induces long-lasting mechanical hypersensitivity in vagal nodose C-fibers. However, the roles of mast cell mediators and downstream ion channels in this process are unclear. ⋯ This was mimicked by PAR2-activating peptide, which sustained for 90 min after wash, but not by PAR2 reverse peptide. TRPA1 inhibitor HC-030031 pretreatment significantly inhibited mechanical hypersensitivity induced by either mast cell activation or PAR2 agonist. Collectively, our data provide new evidence that sensitizing TRPA1 via a PAR2-dependent mechanism plays an important role in mast cell activation-induced mechanical hypersensitivity of vagal nodose C-fibers in guinea pig esophagus.
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Central neuroimmune activation contributes to the initiation and maintenance of neuropathic pain after nerve injury. The current study was aimed to examine the modulation of neuroimmune activation in the spinal cord by the alpha(2) adrenoceptor agonist, clonidine, in a rat model of neuropathic pain induced by partial sciatic nerve ligation (PSNL). Animals were randomly assigned into 6 groups: sham-operation with 20 microg clonidine or saline; and PSNL with clonidine (5, 10, and 20 microg) or saline. ⋯ Administration of clonidine resulted in a dose-dependent attenuation in PSNL-induced mechanical and thermal hyperalgesia. Furthermore, clonidine could markedly inhibit neuroimmune activation characterized by glial activation, production of cytokines, NF-kappaB activation as well as p38 activation. The antihyperalgesic effect of intrathecal clonidine in rats receiving PSNL might partly attribute to the inhibition of neuroimmune activation associated with the maintenance of neuropathic pain.
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Despite the clear roles played by peroxisome proliferators-activated receptor alpha (PPAR-alpha) in lipid metabolism, inflammation and feeding, the effects of its activation in the central nervous system (CNS) are largely unknown. Palmitoylethanolamide (PEA), a member of the fatty-acid ethanolamide family, acts peripherally as an endogenous PPAR-alpha agonist, exerting analgesic and anti-inflammatory effects. Both PPAR-alpha and PEA are present in the CNS, but the specific functions of this lipid and its receptor remain to be clarified. ⋯ To investigate the mechanism by which PEA attenuated hyperalgesia, we evaluated inhibitory kB-alpha (IkB-alpha) degradation and p65 nuclear factor kB (NF-kappaB) activation in DRG. PEA prevented IkB-alpha degradation and p65 NF-kappaB nuclear translocation, confirming the involvement of this transcriptional factor in the control of peripheral hyperalgesia. These results add further support to the broad-spectrum of biological and pharmacological effects induced by PPAR-alpha agonists, suggesting a centrally mediated component for these drugs in controlling inflammatory pain.