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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic neuropathy is a common form of peripheral neuropathy, yet the mechanisms responsible for pain in this disease are poorly understood. Alterations in the expression and function of voltage-gated tetrodotoxin-resistant (TTX-R) sodium channels have been implicated in animal models of neuropathic pain, including models of diabetic neuropathy. We investigated the expression and function of TTX-sensitive (TTX-S) and TTX-R sodium channels in dorsal root ganglion (DRG) neurons and the responses to thermal hyperalgesia and mechanical allodynia in streptozotocin-treated rats between 4-8 weeks after onset of diabetes. Diabetic rats demonstrated a significant reduction in the threshold for escape from innocuous mechanical pressure (allodynia) and a reduction in the latency to withdrawal from a noxious thermal stimulus (hyperalgesia). Both TTX-S and TTX-R sodium currents increased significantly in small DRG neurons isolated from diabetic rats. The voltage-dependent activation and steady-state inactivation curves for these currents were shifted negatively. TTX-S currents induced by fast or slow voltage ramps increased markedly in neurons from diabetic rats. Immunoblots and immunofluorescence staining demonstrated significant increases in the expression of Na(v)1.3 (TTX-S) and Na(v) 1.7 (TTX-S) and decreases in the expression of Na(v) 1.6 (TTX-S) and Na(v)1.8 (TTX-R) in diabetic rats. The level of serine/threonine phosphorylation of Na(v) 1.6 and In Na(v)1.8 increased in response to diabetes. addition, increased tyrosine phosphorylation of Na(v)1.6 and Na(v)1.7 was observed in DRGs from diabetic rats. These results suggest that both TTX-S and TTX-R sodium channels play important roles and that differential phosphorylation of sodium channels involving both serine/threonine and tyrosine sites contributes to painful diabetic neuropathy.
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PMID:Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat. 1512 45

Diabetic neuropathy typically present as a mixture of sensory, motor and autonomic involvement. The development and severity of the neuropathy varies. This article briefly reviews the types of diabetic neuropathy and their relationship to pain and discusses the proposed etiologies.
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PMID:Diabetic neuropathy: the painful foot. 1516 79

Diabetic neuropathy is one of the most frequent peripheral neuropathies associated with hyperalgesia and hyperesthesia. Besides alteration in the levels of neurotransmitter, alteration in the neuronal nitric oxide synthase (nNOS) is a key factor in the pathogenesis of diabetic neuropathy. The present study was aimed at evaluating the role of PDE-5 inhibitor on nociception in streptozotocin-induced diabetes in animal models of nociception (writhing assay in mice and paw hyperalgesia test in rats). Diabetic animals showed a significant decrease in pain threshold as compared to non-diabetic animals in both tests, indicating diabetes induced hyperalgesia in mice and rats. The PDE-5 inhibitor, sildenafil, significantly increased the pain threshold in both diabetic and non-diabetic animals. However, L-NAME, a non-specific NOS inhibitor and methylene blue (MB), a guanylate cyclase inhibitor blocked the antinociceptive effect. The per se administration of L-NAME or MB augmented the hyperalgesic response in diabetic animals with little or no effect in non-diabetic animals, indicating the alteration of NO-cGMP pathway in diabetes. The results in the present study demonstrate that the decreased nNOS-cGMP system may play a crucial role in the pathogenesis of diabetic neuropathy.
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PMID:Modulatory effect of the PDE-5 inhibitor sildenafil in diabetic neuropathy. 1545 68

Diabetic neuropathy occurs in a stocking and glove distribution consistent with a systemic metabolic disease. Historically, this concept led to the conclusion that the only role for surgery in a patient with diabetic neuropathy is for treatment of wounds, amputation, or reconstruction of a Charcot foot. This article reviews the basic scientific and clinical research that support the concepts that metabolic neuropathy renders the peripheral nerve susceptible to compression in patients with diabetes and that decompression of lower extremity peripheral nerves in these patients can relieve pain, restore sensation, and prevent ulceration and amputation.
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PMID:Diabetic neuropathy: review of a surgical approach to restore sensation, relieve pain, and prevent ulceration and amputation. 1556 8

Diabetic neuropathy is common, related to increased morbidity and mortality, and has no effective treatment at present. Interventions based on putative pathways thought to contribute to damage and repair of nerve fibres have yielded little success to date. Pain is a potentially debilitating manifestation of diabetic neuropathy and has many potential sites of origin and, hence, modulation. Its cause is unclear and it does not respond well to traditional pain therapies, proposed to mediate their benefits via multiple peripheral and central mechanisms. A better understanding of the mechanisms leading to nerve fibre degeneration and regeneration as well as pain has recently resulted in the development of a more targeted approach to the treatment of diabetic neuropathy. Thus, specific NMDA receptor antagonists and more specific neuronal serotonin and norepinephrine (noradrenaline) uptake inhibitors offer promise in the treatment of painful diabetic neuropathy. A number of treatments which include the aldose reductase inhibitors and neurotrophins have failed to reach the clinical arena. However, the antioxidant alpha-lipoic acid, as well as compounds which correct vascular dysfunction and hence neuropathy, such as ACE inhibitors and protein kinase C-beta inhibitors, have demonstrated more success.
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PMID:Current and future strategies for the management of diabetic neuropathy. 1598 43

Diabetic neuropathy (DN) refers to symptoms and signs of neuropathy in a patient with diabetes in whom other causes of neuropathy have been excluded. Distal symmetrical neuropathy is the commonest accounting for 75% DN. Asymmetrical neuropathies may involve cranial nerves, thoracic or limb nerves; are of acute onset resulting from ischaemic infarction of vasa nervosa. Asymmetric neuropathies in diabetic patients should be investigated for entrapment neuropathy. Diabetic amyotrophy, initially considered to result from metabolic changes, and later ischaemia, is now attributed to immunological changes. For diagnosis of DN, symptoms, signs, quantitative sensory testing, nerve conduction study, and autonomic testing are used; and two of these five are recommended for clinical diagnosis. Management of DN includes control of hyperglycaemia, other cardiovascular risk factors; alpha lipoic acid and L carnitine. For neuropathic pain, analgesics, non-steroidal anti-inflammatory drugs, antidepressants, and anticonvulsants are recommended. The treatment of autonomic neuropathy is symptomatic.
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PMID:Diabetic neuropathy. 1646 71

Diabetic neuropathy is a very common complication of diabetes mellitus, and animal studies have contributed tremendously to its understanding. The aim of this study was to estimate the neuropathic alterations in the Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus. For this purpose, four groups of animals were used: untreated OLETF rats, sucrose-fed for 2 months OLETF rats, untreated Long-Evans Tokushima Otsuka (LETO) nondiabetic rats as genetic controls of OLETF, and sucrose-fed LETO rats. All were examined at baseline, at the end of the sucrose treatment, and during a washout period. The following parameters were evaluated: motor nerve conduction velocity (MNCV), sensitivity to noxious thermal and mechanical stimuli using the tail-flick (TF) and tail-pressure (TP) tests, and blood glucose (BG) and HbA1c levels. Our results showed that BG and HbA1c were significantly higher in OLETF rats when compared with those in control LETO rats. Sucrose caused remarkable increase of BG and HbA1c in the OLETF rats, but not in the sucrose-fed LETO rats. MNCV and thermal nociception significantly decreased in OLETF rats in their 10th month, while the values of the TP test did not differ compared with those from LETO rats. Sucrose administration significantly decreased the MNCV, and increased the pain threshold evaluated by the TF and TP tests, compared with those in the control OLETF rats. The studied parameters were not significantly altered in sucrose-fed LETO rats. In conclusion, our findings show that signs of diabetic neuropathy appear late in the individual development of the OLETF rats, and MNCV and thermal nociception are selectively affected in this strain. Sucrose deteriorated the diabetic state, decreased MNCV, and caused thermal and mechanical hypoalgesia.
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PMID:Physiological characteristics of diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats. 1654 Nov 92

Diabetic neuropathy is one of the major complications of diabetes mellitus. Small nerve fibers degenerate early in the disease, leading to symptoms ranging from hyperalgesia to loss of pain and temperature sensation. However, the cellular and molecular mechanisms responsible for abnormal pain perception in diabetes have not been identified. Both type-A and type-B endothelin receptors (ETAR and ETBR, respectively) are present in sensory nerves and appear to regulate neuropathic and inflammatory pain. In this study, we compared the expression of endothelin receptors and nociceptive responses in normal and experimentally diabetic rats. Diabetic animals exhibited both an increase in the withdrawal responses to high threshold stimuli (mechanical hyperalgesia) and to light touch stimuli (tactile allodynia). Immunohistochemical and Western blot analysis revealed that diabetic rats have significantly reduced expression of ETBR in sciatic nerves, while no changes were observed in dorsal root ganglia (DRG). In contrast, the expression of ETAR in either sciatic nerves or DRG of diabetic rats was not altered. Importantly, ETBR-deficient transgenic rats showed alterations in pain perception similar to those observed in diabetic rats. These results suggest that changes in the expression of ETBR in peripheral nerve may contribute to the development of mechanical hyperalgesia and tactile allodynia in chronic diabetes.
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PMID:Reduced expression of endothelin B receptors and mechanical hyperalgesia in experimental chronic diabetes. 1680 84

Diabetic neuropathy can affect every organ system of the body. Diagnosis of diabetic neuropathy is usually one of exclusion. Clinical guidelines and the introduction of new medications for pain relief in peripheral neuropathy are improving medical and nursing management. Simpler diagnostic tests for cardiac autonomic neuropathy, which can be performed in an office setting, may mean earlier recognition and treatment with less mortality. Oral medications for the treatment of erectile dysfunction make it easier for the patient to seek treatment for a condition that impact quality of life.
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PMID:Diabetic neuropathies: diagnosis and treatment. 1705 83

Members of the cyclooxygenase (COX) family are known to catalyze the rate-limiting steps of prostaglandins synthesis and reported to be involved in neuropathic pain. Diabetic neuropathy is a type of neuropathic pain, though it is not clear if COX is relevant to the condition. Recently, spinal COX-2 protein was found to be increasing in streptozotocin-induced rats as compared to the constitutive expression. We attempted to determine which cyclooxygenase isoforms are involved in streptozotocin-induced mechanical hyperalgesia, which was induced by a single intraperitoneal injection of 75 mg/kg of streptozotocin. Intrathecal administrations of the COX-2 inhibitors SC-58125 (7-100 microg) and NS-398 (7-60 microg), as well as a high dose (100 microg) of the COX-1 inhibitor SC-560 attenuated hyperalgesia, whereas intrathecal administrations of a low dose (10 microg) of SC-560 and the COX-3 inhibitor acetaminophen (1-7 mg) did not. Further, intrathecal administration of SC-58125 (100 microg) did not produce an analgesic effect in normal rats. These results indicate that intrathecal administration of COX-2 inhibitors has an anti-hyperalgesic effect on streptozotocin-induced mechanical hyperalgesia and we concluded that spinal COX-2 is pivotal in streptozotocin-induced hyperalgesia.
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PMID:Intrathecally administered COX-2 but not COX-1 or COX-3 inhibitors attenuate streptozotocin-induced mechanical hyperalgesia in rats. 1711 5


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