Pain
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Expectancies for pain and pain relief are central to experimental models of placebo analgesia and nocebo hyperalgesia and are a promising target for clinical intervention in patients with chronic pain. Affective states may play an important role in modulating the degree to which expectancies influence pain, broadening the opportunities for intervention targets. However, findings to date have been mixed and mostly limited to laboratory designs. ⋯ Relatedly, higher morning positive affect predicted greater odds of experiencing a match between pain expectancies and pain experience when the expectation was for low, but not high, pain levels (odds ratio = 1.19, confidence interval: 1.01-1.41, P = 0.03). Negative affect, in contrast, did not significantly influence the assimilation of high pain expectancies with high pain experiences. These findings extend previous experimental studies by showing that the association of daily pain expectancies with pain experience varies as a function of affective state.
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The transient receptor potential cation channel subfamily M member-3 (TRPM3) channel is a recently recognized noxious heat sensor that is involved in inflammatory thermal hyperalgesia. To examine its involvement in the development of hyperalgesia in interstitial cystitis/painful bladder syndrome (IC/PBS), rats with cyclophosphamide (CYP)-induced chronic cystitis were used as a model of IC/PBS. Mechanical and thermal hyperalgesia in lower abdominal region overlying the bladder in CYP rats were measured using von Frey filaments and radiant heat, respectively. ⋯ In CYP rats, pretreatment with the TRPM3 antagonist primidone (2 mg/kg, i.p.) significantly alleviated the mechanical and thermal hyperalgesia, bladder submucosal edema, mast cell infiltration, and bladder hyperactivity. Cyclophosphamide-induced cystitis was associated with TRPM3 upregulation at the mRNA, protein, and functional levels in bladder afferent neurons. Our results suggest that upregulation of TRPM3 channels is involved in the development of chronic pain in CYP-induced cystitis, and targeting TRPM3 may be a pharmacological strategy for treating bladder pain in IC/PBS.
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Itch is an unpleasant sensation that evokes a desire to scratch. Pathologic conditions such as allergy or atopic dermatitis produce severe itching sensation. Mas-related G protein receptors (Mrgprs) are receptors for many endogenous pruritogens. ⋯ In vivo Ca 2+ imaging and electrophysiological recording revealed that chloroquine and other agonists of Mrgprs excited DRG neurons via ANO1. More importantly, the overexpression of Ano1 in DRG neurons of Ano1 -deficient mice rescued the impaired itching observed in Ano1 -deficient mice. These results demonstrate that ANO1 mediates the Mrgpr-dependent itch signaling in pruriceptors and provides clues to treating pathologic itch syndromes.