Articles: hyperalgesia.
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This study examined whether peripheral inflammatory injury increases the levels or changes the disposition of substance P (SubP) in the rostral ventromedial medulla (RVM), which serves as a central relay in bulbospinal pathways of pain modulation. Enzyme immunoassay and reverse transcriptase quantitative polymerase chain reaction were used to measure SubP protein and transcript, respectively, in tissue homogenates prepared from the RVM and the periaqueductal gray (PAG) and cuneiform nuclei of rats that had received an intraplantar injection of saline or complete Freund's adjuvant (CFA). Matrix-Assisted Laser Desorption/Ionization Time of Flight analysis confirmed that the RVM does not contain hemokinin-1 (HK-1), which can confound measurements of SubP because it is recognized equally well by commercial antibodies for SubP. ⋯ Tac1 transcripts in homogenates of these nuclei were unchanged four days and two weeks after CFA. These findings suggest that there is an increased mobilization of SubP within processes in the RVM shortly after injury accompanied by an increased synthesis of SubP in neurons that project to the RVM. These findings are consonant with the hypothesis that an increase in SubP release in the RVM contributes to the hyperalgesia that develops after peripheral inflammatory injury.
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P2X3 receptor plays a role in nociception transmission of orofacial pain in temporomandibular disorder patients. A previous study found that P2X3 receptors in masseter muscle afferent neurons and the trigeminal ganglia were involved in masseter muscle pain induced by inflammation caused by chemical agents or eccentric muscle contraction. In this study, we attempted to investigate changes in P2X3 receptors in the trigeminal subnucleus caudalis (Vc) and midbrain periaqueductal gray (PAG) in relation to the hyperalgesia of masseter muscles induced by occlusal interference. ⋯ We found that mechanical pain threshold of bilateral masseter muscles decreased significantly after occlusal interference, which remained for the entire experimental period. The mRNA expression of the P2X3 receptor increased significantly and the number of P2X3R-positive neurons increased markedly in Vc and PAG accordingly. These results indicate that the upregulated expression of P2X3 receptors in Vc and PAG may contribute toward the development of orofacial pain induced by occlusal interference and P2X3 receptors in the PAG may play a key role in the supraspinal antiociception effect.
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Thiazolidinedione drugs (TZDs) such as pioglitazone are approved by the U.S. Food and Drug Administration for the treatment of insulin resistance in type 2 diabetes. However, whether TZDs reduce painful diabetic neuropathy (PDN) remains unknown. Therefore, we tested the hypothesis that chronic administration of pioglitazone would reduce PDN in Zucker Diabetic Fatty (ZDF(fa/fa) [ZDF]) rats. Compared with Zucker Lean (ZL(fa/+)) controls, ZDF rats developed: (1) increased blood glucose, hemoglobin A1c, methylglyoxal, and insulin levels; (2) mechanical and thermal hyperalgesia in the hind paw; (3) increased avoidance of noxious mechanical probes in a mechanical conflict avoidance behavioral assay, to our knowledge, the first report of a measure of affective-motivational pain-like behavior in ZDF rats; and (4) exaggerated lumbar dorsal horn immunohistochemical expression of pressure-evoked phosphorylated extracellular signal-regulated kinase. Seven weeks of pioglitazone (30 mg/kg/d in food) reduced blood glucose, hemoglobin A1c, hyperalgesia, and phosphorylated extracellular signal-regulated kinase expression in ZDF. To our knowledge, this is the first report to reveal hyperalgesia and spinal sensitization in the same ZDF animals, both evoked by a noxious mechanical stimulus that reflects pressure pain frequently associated with clinical PDN. Because pioglitazone provides the combined benefit of reducing hyperglycemia, hyperalgesia, and central sensitization, we suggest that TZDs represent an attractive pharmacotherapy in patients with type 2 diabetes-associated pain. ⋯ To our knowledge, this is the first preclinical report to show that: (1) ZDF rats exhibit hyperalgesia and affective-motivational pain concurrent with central sensitization; and (2) pioglitazone reduces hyperalgesia and spinal sensitization to noxious mechanical stimulation within the same subjects. Further studies are needed to determine the anti-PDN effect of TZDs in humans.
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Case Reports
Dynamic Mechanical Allodynia-One Clinical Sign, Several Mechanisms: Five Illustrative Cases.
Pain evoked by tangential movement across the skin is usually defined as dynamic mechanical allodynia (DMA). Some patients complain of DMA as troublesome as spontaneous pain and refer a marked interfering with activities of daily living and sleep. ⋯ Five exemplificative clinical cases of DMA are presented, each associated to a possible specific mechanism: injured skin DMA, peri-injured skin DMA, far injury DMA, nerve-confined DMA and fear DMA (pseudo allodynia). The identification of these subcategories of DMA can stimulate further studies aimed at evaluating the usefulness of a mechanism-based therapy for the different clinical forms of DMA.
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Temporomandibular disorders (TMD) encompass a variety of dysfunction of the maxillofacial region. A strong relationship between TMD and cervical spine pain exists, and widespread hyperalgesia is common in TMD. This case describes the management and reduction in regional hyperalgesia in a patient with chronic TMD. ⋯ This case described the treatment and reduction of upper extremity hyperalgesia of a patient with chronic jaw and neck pain. Manual therapy may be a valuable intervention in the treatment of chronic TMD with distal hyperalgesia.