The journal of pain : official journal of the American Pain Society
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Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. ⋯ This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain.
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The objective of this study was to assess the quality of websites presenting treatment information for postherpetic neuralgia. The term "postherpetic neuralgia treatment" was searched using the Google and Yahoo search engines. Fifty websites from each were evaluated using the Journal of the American Medical Association (JAMA) benchmarks, the Health on the Net (HON) seal, and the DISCERN instrument. The treatments suggested on each website were compared with 3 recognized first-line treatment options (antidepressants, anticonvulsants, and topical lidocaine). Less than half of the included websites fulfilled all JAMA benchmark requirements. Less than one-third of the websites displayed the HON seal. The DISCERN instrument evaluation revealed that most websites were of moderate quality. Commercial websites tended to be inferior in comparison to noncommercial websites. Most websites recommended at least 2 of the 3 recommended treatments as well as several second- and third-line treatments. One-third to one-half of websites recommended a nonbeneficial treatment. In conclusion, many different postherpetic neuralgia treatments are found on the Internet and patients may be left separating recommended treatments from nonrecommended treatments without help from their healthcare providers. ⋯ This study examined the quality of websites related to postherpetic neuralgia treatment. The results demonstrated that most websites offering advice on postherpetic neuralgia treatment are of only moderate quality and often offer treatment suggestions that are nonbeneficial. Patients and providers must use caution when taking advice from these sites.
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Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified 5 components labeled: 1) heat pain ratings; 2) heat pain aftersensations and tolerance; 3) mechanical cutaneous pain sensitivity; 4) pressure pain thresholds; and 5) heat pain temporal summation. These results demonstrate that compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extracranial body sites, and provide for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures. ⋯ This article describes experimental pain sensitivity differences between a large sample of people with chronic TMD and non-TMD controls, using multiple stimulus modalities and measures. Variability in the magnitude and consistency of case-control differences highlight the need to consider multiple testing measures to adequately assess pain processing alterations in chronic pain conditions.