Articles: hyperalgesia.
-
The transient receptor potential vanilloid receptor type-1 (TRPV1) is critically involved in peripheral nociceptive processes of somatic and visceral pain. However, the role of the capsaicin receptor in the brain regarding visceral pain remains elusive. ⋯ Notably, intracerebral TRPV1 antagonism by SB 366791 significantly reduced chemical and inflammatory spontaneous abdominal nocifensive responses, as observed by reduced expressions of nociceptive facial grimacing, illustrating the affective component of pain. In addition to the established role of cerebral TRPV1 in anxiety, fear, or emotional stress, we demonstrate here for the first time that TRPV1 in the brain modulates visceral nociception by interfering with the affective component of abdominal pain.
-
Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. ⋯ Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9(-/-) mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity, and is essential for activation by noxious inflammatory mediators, including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics.
-
The importance of the modulation of pain by emotion is now widely recognised. In particular, stress and anxiety, depending on their nature, duration and intensity, can exert potent, but complex, modulatory influences typified by either a reduction or exacerbation of the pain state. ⋯ Preclinical studies of SIH are essential for our understanding of the mechanisms underpinning stress-related pain syndromes and for the identification of neural pathways and substrates, and the development of novel therapeutic agents for their clinical management. In this review, we describe clinical and pre-clinical models used to study SIH and discuss the neural substrates, neurotransmitters and neuromodulatory systems involved in this phenomenon.
-
The aim of this study was to determine whether ranolazine, a new medication that targets sodium channels to improve cardiac ischemia and angina, could be an effective analgesic agent for pain associated with demyelination injury. ⋯ Ranolazine exerts broad-spectrum actions to reduce mechanical allodynia that is associated with peripheral demyelination injury.
-
A limited number of quantitative sensory pain tests (QST) were selected on the basis of ease of application and interpretation in a clinical setting. QST results were summarized as a composite score on a scale of 0 to 4 that was deemed to facilitate clinical interpretation. The QST set was used to investigate differences in pain sensitivity between low-back pain (LBP) subgroups and was correlated with important clinical parameters. ⋯ Pain sensitivity may be important for the prognosis of LBP, but QST is not currently part of routine clinical examination of LBP patients. The selected set of pain tests and the composite score of pain sensitivity could serve as a clinically applicable QST procedure in the examination of LBP.