Pain
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Adenosine triphosphate-sensitive potassium (K(ATP)) channels are suggested to be involved in pathogenesis of neuropathic pain, but remain underinvestigated in primary afferents and in the spinal cord. We examined alterations of K(ATP) channels in rat spinal cord and tested whether and how they could contribute to neuropathic pain. The results showed that protein expression for K(ATP) channel subunits SUR1, SUR2, and Kir6.1, but not Kir6.2, were significantly downregulated and associated with thermal hyperalgesia and mechanical allodynia after sciatic nerve injury. ⋯ Furthermore, preadministration of an astroglial gap junction decoupler carbenoxolone (10 μg) completely reversed the inhibitory effects of CRO treatment on the hyperalgesia and allodynia and phosphorylation of NR1 and NR2B receptors and the subsequent activation of Ca(2+)-dependent signals Ca(2+)/calmodulin-dependent kinase II and cyclic adenosine monophosphate (cAMP) response element binding protein. These findings suggest that nerve injury-induced downregulation of the K(ATP) channels in the spinal cord may interrupt the astroglial gap junctional function and contribute to neuropathic pain, thus the K(ATP) channels opener can reduce neuropathic pain probably partly via regulating the astroglial gap junctions. This study may provide a new strategy for treating neuropathic pain using K(ATP) channel openers in the clinic.
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Forebrain medial septum region facilitates nociception in a rat formalin model of inflammatory pain.
The medial septum is anatomically and functionally linked to the hippocampus, a region implicated in nociception. However, the role of medial septum in nociception remains unclear. To investigate the role of the region in nociception in rats, muscimol, a GABA agonist, or zolpidem, a positive allosteric modulator of GABA(A) receptors, was microinjected into medial septum to attenuate the activity of neurons in the region. ⋯ The reduction was accompanied by a decrease in formalin-induced expression of spinal c-Fos protein that serves as an index of spinal nociceptive processing. The drug effects on nociceptive behaviors were without overt sedation and were distinct from the effects observed after septal lateral microinjections. Taken together, these findings suggest that the activation of medial septum is pro-nociceptive and facilitates aspects of central neural processing underlying nociception.
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Early, preemptive blockade of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) attenuates tumor-induced nerve sprouting and bone cancer pain. A critical unanswered question is whether late blockade of NGF/TrkA can attenuate cancer pain once NGF-induced nerve sprouting and neuroma formation has occurred. By means of a mouse model of prostate cancer-induced bone pain, anti-NGF was either administered preemptively at day 14 after tumor injection when nerve sprouting had yet to occur, or late at day 35, when extensive nerve sprouting had occurred. ⋯ In this model, as in most cancers, the individual cancer cell colonies have a limited half-life because they are constantly proliferating, metastasizing, and undergoing necrosis as the parent cancer cell colony outgrows its blood supply. Similarly, the sensory and sympathetic nerve fibers that innervate the tumor undergo sprouting at the viable/leading edge of the parent tumor, degenerate as the parent cancer cell colony becomes necrotic, and resprout in the viable, newly formed daughter cell colonies. These results suggest that preemptive or late-stage blockade of NGF/TrkA can attenuate nerve sprouting and cancer pain.
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Knowledge about functional ability, including activities of daily living (ADL), in patients with chronic widespread pain (CWP) and fibromyalgia (FMS) is largely based on self-report. The purpose of this study was to assess functional ability by using standardised, observation-based assessment of ADL performance and to examine the relationship between self-reported and observation-based measures of disability. A total of 257 women with CWP, 199 (77%) fulfilling the American College of Rheumatology tender point criteria for FMS, were evaluated with the Assessment of Motor and Process Skills (AMPS), an observation-based assessment providing linear measures of ADL motor and ADL process skill ability (unit: logits). ⋯ Only weak to moderate correlations between self-reported functional ability and observation-based AMPS ability measures were observed. The results of the study support the notion of considerable performance difficulties in women with CWP. The everyday life problems are substantial and place the individual at risk of need of support for community living.