Pain
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Widespread sensory hypersensitivity is present in acute whiplash and is associated with poor recovery. Decreased nociceptive flexion reflex (NFR) thresholds (spinal cord hyperexcitability) are a feature of chronic whiplash but have not been investigated in the acute to chronic injury stage. This study compared the temporal development of sensory hypersensitivity and NFR responses from soon after injury to either recovery or to transition to chronicity. ⋯ In contrast generalized sensory hypersensitivity (pressure and cold) was only ever present in those with persistent moderate/severe symptoms and remained unchanged throughout the study period. This suggests different mechanisms underlie sensory hypersensitivity and NFR responses. In multivariate analyses only initial NDI scores (p=0.003) were a unique predictor of persistent spinal cord hyperexcitability indicating possible ongoing peripheral nociception following whiplash injury.
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For musculoskeletal disorders like low back pain and fibromyalgia, evidence is growing for fear of movement to play an important role in the development of chronic pain. In temporomandibular disorder (TMD) patients, however, this construct has not received any attention yet. Therefore, in this paper, (1) a generally used instrument to measure fear of movement, the Dutch version of the Tampa Scale for Kinesiophobia (TSK), was adapted for its use in TMD patients (and translated for equivalence to English), (2) the psychometric properties of the Dutch version of the TSK-TMD were assessed, and (3) the association of various symptoms of TMD (i.e., pain, joint sounds, and limited jaw movements) with fear of movement was evaluated. ⋯ Multiple regression analysis showed that TMD functional problems (i.e., temporomandibular joint sounds or a stuck/locked feeling) were more strongly associated with fear of movement than with pain. This finding leads to new perspectives regarding the interplay between musculoskeletal complaints, cognition, and avoidance behavior. The results provide a basis for use of the 12-item version for routine assessment of fear of movement in TMD patients, and for future clinical studies, for example, to the role of fear of movement in TMD-treatment success.
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In patients with distal symmetric polyneuropathy we assessed non-nociceptive Abeta- and nociceptive Adelta-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Abeta-fibre function, and laser-evoked potentials (LEPs) to assess Adelta-fibre function. ⋯ In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds.
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The enzyme 3alpha-hydroxysteroid oxido-reductase (3alpha-HSOR) catalyzes the synthesis and bioavailability of 3alpha,5alpha-neurosteroids as allopregnanolone (3alpha,5alpha-THP) which activates GABA(A) receptors and blocks T-type calcium channels involved in pain mechanisms. Here, we used a multidisciplinary approach to demonstrate that 3alpha-HSOR is a cellular target the modulation of which in dorsal root ganglia (DRG) may contribute to suppress pain resulting from peripheral nerve injury. Immunohistochemistry and confocal microscope analyses showed 3alpha-HSOR-immunostaining in naive rat DRG sensory neurons and glial cells. ⋯ Most importantly, in vivo knockdown of 3alpha-HSOR expression in healthy rat DRG using 6-carboxyfluorescein-3alpha-HSOR-siRNA exacerbated thermal and mechanical pain perceptions. This paper is the first to show that siRNA-induced knockdown of a key neurosteroid-synthesizing enzyme directly affects an important function as nociception. Hopefully, these results may be useful for the development of novel analgesics.
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Anti-nociceptive tolerance to opioids is a well-described phenomenon, which severely limits the clinical efficacy of opioids for the treatment of chronic pain syndromes. The mechanisms that drive anti-nociceptive tolerance, however, are less well understood. We have previously shown that glia have a central role in the development of morphine tolerance and that administration of a glial modulating agent attenuated tolerance formation. ⋯ P2X4 receptor asODN treatment also attenuated the morphine-dependent increase of spinal ionized calcium binding protein (Iba1), glial fibrillary acidic protein (GFAP) and mu opioid receptor protein expression. Chronic morphine also decreased perivascular microglial ED2 expression, which was reversed by P2X4 receptor asODN. Together, these data suggest that the modulation of P2X4 receptor expression on microglia and perivascular microglia may prove an attractive target for adjuvant therapy to attenuate opioid-induced anti-nociceptive tolerance.