Pain
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The gastrointestinal (GI) tract is a system of organs within multicellular animals which facilitates the ingestion, digestion, and absorption of food with subsequent defecation of waste. A complex arrangement of nerves and ancillary cells contributes to the sensorimotor apparatus required to subserve such essential functions that are with the exception of the extreme upper and lower ends of the GI tract normally subconscious. ⋯ Although this function can be protective, when dysregulated, particularly on a chronic basis, the same system can lead to considerable morbidity. The anatomical and molecular basis of gastrointestinal nociception, conditions associated with chronic unexplained visceral pain, and developments in treatment are presented in this review.
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Osteoarthritis (OA) is a debilitating and painful disease, the incidence of which increases with advancing age. One of the confounding aspects of OA is that there is a disconnect between the severity of joint degeneration and the intensity of pain reported. This study examined the relationship between age, joint nociception, and joint pathology in an animal model of naturally occurring OA. ⋯ Micro-CT and histopathological determination of OA positively correlated with age; however, there was no significant correlation between the severity of joint degeneration and nociception. In the Dunkin Hartley model of inveterate OA, the level of joint pathology correlates well with increasing age. This study also provides the first objective evidence that there is no correlation between joint nociception and articular damage, thereby corroborating the clinical observation that pain is a poor predictor of OA severity.
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We investigated the efficacy of local intraplantar (i.pl.) injection of peptide and non-peptide mu-, delta- and kappa-opioid receptor agonists in rat models of inflammatory and neuropathic pain. Locally applied agonists dose-dependently reduced formalin-induced flinching of the inflamed paw and induced antiallodynic and antihyperalgesic effects in sciatic nerve ligation-induced neuropathic pain. These effects were mediated by peripheral opioid receptors localized at the side of tissue/nerve injury, as was demonstrated by selective and non-selective opioid receptors antagonists. ⋯ Furthermore, in order to assess whether adaptations in the expression of opioid genes could underlie the clinical observation of reduced opioid effectiveness in neuropathic pain, we analyzed the abundance of opioid transcripts in the spinal cord and dorsal root ganglia (DRG) during the neuropathy and inflammation. Nerve injury down-regulated mRNA for all types of opioid receptors in the DRG, which is predicted to decrease in the synthesis of opioid receptors to possibly account for the reduced effectiveness of locally administered opioids in neuropathy. The obtained results differentiate inflammatory and neuropathic pain and provide a novel insight into the peripheral effectiveness of opioids in both types of pain.
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The most obvious impairments associated with spinal cord injury (SCI) are loss of sensation and motor control. However, many subjects with SCI also develop persistent neuropathic pain below the injury which is often severe, debilitating and refractory to treatment. The underlying mechanisms of persistent neuropathic SCI pain remain poorly understood. ⋯ The amount of S1 reorganization in subjects with SCI significantly correlated with on-going pain intensity levels. This study provides evidence of a link between the degree of cortical reorganization and the intensity of persistent neuropathic pain following SCI. Strategies aimed at reversing somatosensory cortical reorganization may have therapeutic potential in central neuropathic pain.