Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complete nerve transection results in loss of sensation and paralysis of the involved extremity. Such injury drastically reduces content of the nociceptive peptides, substance P, and somatostatin in the dorsal horn of the spinal cord and dorsal root ganglia innervating the limb. Partial nerve injuries occur more commonly in clinical practice, however, and frequently result in the development of chronic neuropathic pain. To investigate mechanisms underlying this pathologic pain syndrome, rats were subjected to partial sciatic nerve transection. Withdrawal thresholds determined with Von Frey hairs dropped dramatically in the operated limb. On postoperative Day 4, thresholds had decreased from 15 g to less than 5 g on the operated side, whereas those on the contralateral (unoperated) side or those from sham-operated rats did not change. Sciatic hemisection had no effect on total content of either substance P or somatostatin in the dorsal spinal cord and lumbar dorsal root ganglia as measured by radioimmunoassay on postoperative Days 4, 7, or 14. However, when examined immunohistochemically, there was a marked redistribution of both peptides associated with partial transection. On the contralateral side or in sham-operated rats, both substance P and somatostatin were confined to the superficial laminae of the dorsal horn. By contrast, on the operated side, content of both peptides was reduced by more than half in the superficial laminae. There was a compensatory increase in content in the deeper laminae where nociceptive peptides are not usually found. Redistribution of substance P and somatostatin may be due to axonal sprouting, increased peptide expression by interneurons, or aberrant expression of nociceptive peptides by neurons normally mediating mechanical sensation. The presence of increased levels of nociceptive peptides in regions of the spinal cord that mediate innocuous sensation may underlie development of allodynia.
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PMID:Partial sciatic nerve transection causes redistribution of pain-related peptides and lowers withdrawal threshold. 1524 43

Characterization and differentiation of joint pain is difficult. Though degenerative changes in joints are frequent causes of pain in hip and knee, these changes are not always painful, and other possible causes of pain must also be considered. In degenerative changes in the spine, the problem is even more complex, as peripheral neuropathic pain, caused by mechanical compression and/or leakage of cytokines irritating nerve roots may be difficult to differentiate from nociceptive pain from intervertebral joints, discs or muscles. We know now that nociceptive pain has often referred to areas of pain with numbness and parestesthethic sensations, previously regarded as characteristic for neurogenic pain. Furthermore, in patients with painful coxarthrosis quantitative sensory testing (QST) has shown disturbed sensory thresholds not only in regions adjacent to the affected hip but also contralaterally. These sensory disturbances, previously noted in neuropathic pain, normalized after successful surgery with relief of pain, thus confirming the relation to the hip joint. Patients with painful coxarthrosis also have moderately increased substance P activity in cerebrospinal fluid. Thus the findings show some similarities with fibromyalgic patients with highly increased substance P in cerebrospinal fluid and sensory disturbances. In conclusion, joint pain has a profound impact on the sensory system and need a multimodal approach.
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PMID:Characterization of joint pain in human OA. 1528 46

Dental treatments sometimes cause sensory impairment, especially in the region innervated by the third division of the trigeminal nerve. The most frequent symptoms are loss of sensation and abnormal sensation. Although most studies have addressed the neuropathic symptom "allodynia" using experimental animal models of the infraorbital nerve, there is little information regarding the sensory impairment that frequently occurs clinically. Therefore, different experimental models are required to clarify the mechanisms of the clinical effects, and previous experimental models have been limited to rats. Here, we report a sensory impairment model in mice whose mechanical touch threshold increased after tight ligation of the mental nerve. Habituation before surgery by mechanical touching of the face enabled us to observe the long-term chronological changes in sensation. The mechanical touch thresholds within the mental nerve region were measured for 70 postoperative (PO) days. Changes in the distribution of substance P (SP) were evaluated by immunohistochemistry to clarify the involvement of axonal flow in the sensory impairment and its recovery. The mechanical touch thresholds transiently increased by PO days 2-3, but decreased to the preoperative levels at around PO day 14. Apparent SP immunoreactivity was recognizable on the medial side to the ligation at PO days 2-3 and disappeared at PO day 7. These behavioural and immunohistochemical changes appeared to exhibit similar time courses, suggesting a possible relationship between them. Therefore, we suggest that our experimental mouse model could represent a new model for clarifying the mechanism of the sensory impairment caused by peripheral nerve injury.
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PMID:Behavioural and histological observations of sensory impairment caused by tight ligation of the trigeminal nerve in mice. 1940 17

Our understanding of the role of somatosensory feedback in regulating motility during chicken embryogenesis and fetal development in general has been hampered by the lack of an approach to selectively alter specific sensory modalities. In adult mammals, pyridoxine overdose has been shown to cause a peripheral sensory neuropathy characterized by a loss of both muscle and cutaneous afferents, but predominated by a loss of proprioception. We have begun to explore the sensitivity of the nervous system in chicken embryos to the application of pyridoxine on embryonic days 7 and 8, after sensory neurons in the lumbosacral region become post-mitotic. Upon examination of the spinal cord, dorsal root ganglion and peripheral nerves, we find that pyridoxine causes a loss of neurotrophic tyrosine kinase receptor type 3-positive neurons, a decrease in the diameter of the muscle innervating nerve tibialis, and a reduction in the number of large diameter axons in this nerve. However, we found no change in the number of Substance P or calcitonin gene-related peptide-positive neurons, the number of motor neurons or the diameter or axonal composition of the femoral cutaneous nerve. Therefore, pyridoxine causes a peripheral sensory neuropathy in embryonic chickens largely consistent with its effects in adult mammals. However, the lesion may be more restricted to proprioception in the chicken embryo. Therefore, pyridoxine lesion induced during embryogenesis in the chicken embryo can be used to assess how the loss of sensation, largely proprioception, alters spontaneous embryonic motility and subsequent motor development.
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PMID:Teratogenic effects of pyridoxine on the spinal cord and dorsal root ganglia of embryonic chickens. 2559 28

Peripheral neuropathy is a common adverse effect of paclitaxel and oxaliplatin treatment. The major dose-limiting side effect of these drugs is peripheral sensory neuropathy. The symptoms of paclitaxel-induced neuropathy are mostly sensory and peripheral in nature, consisting of mechanical allodynia/hyperalgesia, tingling, and numbness. Oxaliplatin-induced neurotoxicity manifests as rapid-onset neuropathic symptoms that are exacerbated by cold exposure and as chronic neuropathy that develops after several treatment cycles. Although many basic and clinical researchers have studied anticancer drug-induced peripheral neuropathy, the mechanism is not well understood. In this review, we focus on (1) analysis of transient receptor potential vanilloid 1 (TRPV1) channel expression in the rat dorsal root ganglion (DRG) after paclitaxel treatment and (2) analysis of transient receptor potential ankyrin 1 (TRPA1) channel in the DRG after oxaliplatin treatment. This review describes that (1) paclitaxel-induced neuropathic pain may be the result of up-regulation of TRPV1 in small- and medium-diameter DRG neurons. In addition, paclitaxel treatment increases the release of substance P, but not calcitonin gene-related peptide, in the superficial layers of the spinal dorsal horn. (2) TRPA1 expression via activation of p38 mitogen-activated protein kinase in small-diameter DRG neurons, at least in part, contributes to the development of oxaliplatin-induced acute cold hyperalgesia. We suggest that TRPV1 or TRPA1 antagonists may be potential therapeutic lead compounds for treating anticancer drug-induced peripheral neuropathy.
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PMID:[Role of Transient Receptor Potential Channels in Paclitaxel- and Oxaliplatin-induced Peripheral Neuropathy]. 2683 7