Articles: hyperalgesia.
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Nonsense-mediated messenger RNA (mRNA) decay increases targeted mRNA degradation and has been implicated in the regulation of gene expression in neurons. The authors hypothesized that nonsense-mediated μ-opioid receptor mRNA decay in the spinal cord is involved in the development of neuropathic allodynia-like behavior in rats. ⋯ This study suggests that phosphorylated UPF1-dependent nonsense-mediated μ-opioid receptor mRNA decay is involved in the pathogenesis of neuropathic pain.
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Complex regional pain syndrome (CRPS) is associated with a range of sensory disturbances on the symptomatic side of the body but whether this includes olfaction is uncertain. To clarify this, the aims of this study were to compare ratings of intensity and hedonic appeal of household odorants in CRPS patients and controls, and to determine whether ratings differed between the symptomatic and contralateral sides within the sample of patients. ⋯ These findings suggest that the trigeminal component of olfaction interacts bilaterally with pain-sensitized circuits in the thalamus or higher cortical centers to distort odor perception in patients with CRPS. This aberrant process appears to differ from the mechanism that underlies hemilateral hyperalgesia in other sensory modalities.
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Despite the available knowledge on underlying mechanisms and the development of several therapeutic strategies, optimal management of postoperative pain remains challenging. This preclinical study hypothesizes that, by promoting an anti-inflammatory scenario, pre-emptive administration of IMT504, a noncoding, non-CpG oligodeoxynucleotide with immune modulating properties, will reduce postincisional pain, also facilitating therapeutic opioid-sparing. Male adult Sprague-Dawley rats with unilateral hindpaw skin-muscle incision received pre-emptive (48 and 24 hours prior to surgery) or postoperative (6 hours after surgery) subcutaneous vehicle (saline) or IMT504. ⋯ Altogether, pre-emptive or postoperative IMT504 provides protection against postincisional pain, through participation of significant immunomodulatory actions, and exhibiting opioid-sparing effects. PERSPECTIVE: This preclinical study introduces the noncoding non-CpG oligodeoxynucleotide IMT504 as a novel modulator of postoperative pain and underlying inflammatory events. The opioid-sparing effects observed for IMT504 appear as a key feature that could contribute, in the future, to reducing opioid-related adverse events in patients undergoing surgical intervention.
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Randomized Controlled Trial
Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction.
The current paper explores the psychological predictors of nocebo hyperalgesia and whether the reduction of nocebo hyperalgesia can be predicted by susceptibility to nocebo hyperalgesia and psychological characteristics. ⋯ Our findings suggest that open-label conditioning leads to stronger nocebo hyperalgesia when trait anxiety is high and dispositional optimism is low, while these psychological characteristics, along with larger nocebo hyperalgesia, also predict open-label counterconditioning to be an effective nocebo-reduction strategy. Susceptibility to nocebo hyperalgesia, trait anxiety, and dispositional optimism might be indicators of a flexible pain regulatory system.
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Stress plays a major role in the symptom burden of oncology patients and can exacerbate cancer chemotherapy-induced peripheral neuropathy (CIPN), a major adverse effect of many classes of chemotherapy. We explored the role of stress in the persistent phase of the pain induced by oxaliplatin. Oxaliplatin induced hyperalgesic priming, a model of the transition to chronic pain, as indicated by prolongation of hyperalgesia produced by prostaglandin E 2 , in male rats, which was markedly attenuated in adrenalectomized rats. ⋯ Furthermore, antisense for protein kinase C epsilon, a second messenger involved in type I hyperalgesic priming, also attenuated oxaliplatin-induced hyperalgesic priming. Inhibitors of second messengers involved in the maintenance of type I (cordycepin) and type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN.