Articles: hyperalgesia.
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Patients suffering with functional somatic pain syndromes such as temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS) have some similar symptoms, but the underlying cause is still unclear. The purpose of this study was to investigate whether 5-HT2A and 5-HT2C receptors in the spinal cord contribute to somatic hyperalgesia induced by orofacial inflammation combined with different modes of stress. Ovariectomized rats were injected subcutaneously with estradiol and bilateral masseter muscles were injected with complete Freund's adjuvant followed by stress. ⋯ The expression of 5-HT2A and 5-HT2C receptors significantly decreased in the orofacial inflammation combined with stress groups. Intrathecal injection of 5-HT2A or 5-HT2C receptor agonist reversed somatic hyperalgesia. The results suggest that down-regulation of 5-HT2A and 5-HT2C receptors in the spinal cord contributes to somatic hyperalgesia induced by orofacial inflammation combined with stress, indicating that 5-HT2A and 5-HT2C receptors may be potential targets in the treatment of TMD comorbid with FMS.
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Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being developed. However, because the mechanism(s) underlying medication overuse headache are not well understood, it is difficult to predict whether any particular acute medication will induce MOH in susceptible individuals. LY573144 (lasmiditan), a 5-HT1F receptor agonist, has recently been shown to be effective in the acute treatment of migraine in phase 3 trials. The aim of this study is to determine whether frequent administration of lasmiditan induces behaviors consistent with MOH in a pre-clinical rat model. ⋯ In a pre-clinical rat model of MOH, oral lasmiditan, like sumatriptan, induced acute transient cutaneous allodynia in the periorbital and hindpaw regions that after resolution could be re-evoked by putative migraine triggers. These results suggest that lasmiditan has the capacity to induce MOH through persistent latent peripheral and central sensitization mechanisms.
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Oxaliplatin frequently causes severe peripheral neuropathy as a dose-limiting toxicity. However, this toxicity lacks a strategy for prevention. Cystine/Theanine is a supplement, which includes precursors for the biosynthesis of glutathione. ⋯ Moreover, co-administration of Cystine and Theanine to rats significantly increased the glutathione level in the sciatic nerve compared with the oxaliplatin group. Furthermore, Cystine and Theanine did not attenuate the tumour cytotoxicity of oxaliplatin in C-26 tumour cell-bearing mice. These findings suggest that Cystine and Theanine may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.
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We have previously shown that endogenous adenosine 5'-triphosphate (ATP), via P2X3 and P2X2/3 receptors, plays an essential role in carrageenan-induced articular hyperalgesia model in rats' knee joint. In the present study, we used the rat knee joint incapacitation test, Enzyme-Linked Immunosorbent Assay (ELISA), and myeloperoxidase enzyme activity assay, to test the hypothesis that the activation of P2X3 and P2X2/3 receptors by their agonist induces articular hyperalgesia mediated by the inflammatory mediators bradykinin, prostaglandin, sympathomimetic amines, pro-inflammatory cytokines and by neutrophil migration. We also tested the hypothesis that the activation of P2X3 and P2X2/3 receptors contributes to the articular hyperalgesia induced by the inflammatory mediators belonging to carrageenan inflammatory cascade. ⋯ Moreover, the co-administration of A-317491 significantly reduced the articular hyperalgesia induced by bradykinin, prostaglandin E2 (PGE2), and dopamine. These findings suggest that peripheral P2X3 and P2X2/3 receptors activation induces articular hyperalgesia by an indirect sensitization of the primary afferent nociceptor of rats' knee joint through the release of inflammatory mediators. Further, they also indicate that the activation of these purinergic receptors by endogenous ATP mediates the bradykinin-, PGE2-, and dopamine-induced articular hyperalgesia.
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Randomized Controlled Trial
Learning mechanisms in nocebo hyperalgesia: the role of conditioning and extinction processes.
Nocebo hyperalgesia is a clinically relevant phenomenon and may be formed as a result of associative learning, implemented by classical conditioning. This study explored for the first time distinct nocebo conditioning methods and their consequences for nocebo attenuation methods. Healthy participants (N = 140) were recruited and randomized to the following nocebo hyperalgesia induction groups: conditioning with continuous reinforcement (CRF), conditioning with partial reinforcement (PRF), and a sham-conditioning control group. ⋯ However, compared with CRF, conditioning with PRF resulted in more resistance to counterconditioning. These findings demonstrate that the more ambiguous learning method of PRF can induce nocebo hyperalgesia and may potentially explain the treatment resistance and chronification seen in clinical practice. Further research is required to establish whether attenuation with counterconditioning is generalizable to clinical settings.