Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both myelinated and unmyelinated afferents are implicated in transmitting diabetic neuropathic pain. Although unmyelinated afferents are generally considered to play a significant role in diabetic neuropathic pain, pathological changes in diabetic neuropathy occur mostly in myelinated A-fibers. In the present study, we first examined the role of capsaicin-sensitive C-fibers in the development of allodynia induced by diabetic neuropathy. We then studied the functional changes of afferent nerves pertinent to diabetic neuropathic pain. Diabetes was induced in rats by i.p. streptozotocin. To deplete capsaicin-sensitive C-fibers, rats were treated with i.p. resiniferatoxin (300 microg/kg). Mechanical and thermal sensitivities were measured using von Frey filaments and a radiant heat stimulus. Single-unit activity of afferents was recorded from the tibial nerve. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic rats. Resiniferatoxin treatment did not alter significantly the degree and time course of allodynia. Post-treatment with resiniferatoxin also failed to attenuate allodynia in diabetic rats. The electrophysiological recordings revealed ectopic discharges and a higher spontaneous activity mainly in Adelta- and Abeta-fiber afferents in diabetic rats regardless of resiniferatoxin treatment. Furthermore, these afferent fibers had a lower threshold for activation and augmented responses to mechanical stimuli. Thus, our study suggests that capsaicin-sensitive C-fiber afferents are not required in the development of allodynia in this rat model of diabetes. Our electrophysiological data provide substantial new evidence that the abnormal sensory input from Adelta- and Abeta-fiber afferents may play an important role in diabetic neuropathic pain.
 ...
PMID:Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats. 1220 99

Mechanical hyperalgesia is an early symptom of diabetic neuropathy. To evaluate the mechanisms underlying this symptom, it was studied and compared in rat models of systemic and local hyperglycemia. Systemic hyperglycemia was induced by a single injection of streptozotocin (STZ, 50 mg/kg). Local hyperglycemia either in L(5) dorsal root ganglion (DRG) or a segment of the sciatic nerve at mid-thigh level was maintained by perfusion with 30-mM glucose solution delivered from a surgically implanted osmotic minipump. Mechanical hyperalgesia was assessed using modified von Frey filaments and hind limb withdrawal threshold measurements. During 2 weeks of STZ-induced diabetes rat systemic blood glucose level increased from 5.1+/-0.3 to 23+/-1.9 mM and limb withdrawal threshold decreased by approximately 30% bilaterally. During 2 weeks of local perfusion systemic blood glucose did not change; however, rats that underwent perfusion of the DRG or sciatic nerve with glucose exhibited a rapid (completed in approximately 1 week) 40-50% decrease in ipsilateral limb withdrawal threshold. Perfusion of the sciatic nerve with the normoglycemic buffer solution did not affect withdrawal thresholds. The aldose reductase inhibitor sorbinil (2.5 mg/ml) when added to 30-mM glucose perfusion solution prevented hyperalgesia. These data suggest that mechanical hyperalgesia in diabetic animals may, at least in part, result from focal injury caused by a direct toxic effect of glucose in the peripheral nervous system. These data also support the idea of activation of aldose reductase and polyol pathway as an important mechanism of hyperglycemia-induced impairment of nerve function.
 ...
PMID:Mechanical hyperalgesia in rat models of systemic and local hyperglycemia. 1250 70

Spinally administered muscarinic receptor agonists or acetylcholinesterase inhibitors can produce antinociception. However, the mechanisms of the action of cholinergic agents in the spinal cord are not fully understood. Activation of spinal muscarinic receptors evokes gamma-aminobutyric acid (GABA) release, which reduces the glutamatergic synaptic input to dorsal horn neurons through GABA(B) receptors. In this study, we determined the functional role of spinal GABA(B) receptors in the antinociceptive action of intrathecal cholinergic agents in normal rats and in a rat model of diabetic neuropathic pain. Diabetes was induced by intraperitoneal streptozotocin in rats. The intrathecal catheter was inserted with its tip positioned at the lumbar spinal level. Nociceptive threshold was measured by the paw withdrawal latency in response to a radiant heat stimulus in normal rats. Mechanical allodynia in diabetic rats was determined by von Frey filaments applied to the hindpaw. The effect of intrathecal muscarine or neostigmine was examined through pretreatment with the specific GABA(B) receptor antagonist, CGP55845, or its vehicle. Intrathecal injection of muscarine or neostigmine significantly increased the withdrawal latency in response to a heat stimulus in normal rats and the withdrawal threshold in response to application of von Frey filaments in diabetic rats. Intrathecal pretreatment with CGP55845 significantly attenuated the effect of both muscarine or neostigmine in normal rats. Furthermore, the antiallodynic effect of intrathecal neostigmine and muscarine was largely eliminated by CGP55845 in diabetic rats. These data suggest that the GABA(B) receptors in the spinal cord mediate both the antinociceptive and antiallodynic actions of intrathecal muscarine or neostigmine in normal rats and in a rat model of diabetic neuropathic pain. This study provides new functional evidence that activation of spinal GABA(B) receptors is one of the important mechanisms underlying the antinociceptive action of intrathecal cholinergic agents.
 ...
PMID:Spinal GABAB receptors mediate antinociceptive actions of cholinergic agents in normal and diabetic rats. 1259 Nov 21

The First Surgical Clinic of the First Medical Faculty of Charles University and General Faculty Hospital in Prague made operations of the pancreas ever since 1971. In the work sooner or later all approaches to surgical treatment pancreatitis were reflected. The authors present a brief review of results and their own experience since 1994 when duodenum-sparing operations were introduced. Indications for surgical treatment were based on the diagnosis by US, CT and ERCP, in exceptional case MR, after evaluation by a pancreatologist, roentgenologist and surgeon. The group of patients with chronic pancreatitis was extended by 21 patients from a group operated because of preoperative suspicion of a malignant pancreatic tumour not confirmed during and after surgery. In those Whipple's operation was preformed. The same operation was performed in three patients with chronic pancreatitis with serious changes in the area of the head of the pancreas. In 123 patients a drainage and duodenum sparing operation was preformed, of these in 57 according to Beger, 19 according to Frey, 37 Partington-Rochelle's procedure. The authors record two sepsis postoperative complications after the classical Beger operation and the hospital stay was on average by five days shorter as compared with the classical method of Whipple. When evaluating postoperative complaints and problems (pain, malnutrition, physical constitution and social position) the authors recorded equally favourable results as after non-complicated duodenopancreatectomy. They varied, depending on the patients co-operation round 84-87% while authors consider Beger's operation logical because of the removal of the main tissue mass of the head of the pancreas, responsible for pain, complications caused by fibrosis in the area round the bile duct and duodenum, responsible for the deteriation of the compartment syndrome in the left half of the gland. Its result is destruction of the remainder of exocrine and endocrine tissue. Of 187 operated patients one patient with decompensated diabetes died postoperatively. Based on their own experience the authors do not consider repeated re-operations an absolute contraindication of Beger's operation when conditions permit. A problem is, in their opinion, fibrosis in the vicinity of the pancreas and portal overpressure.
 ...
PMID:[Choice of surgical procedure in operations for chronic pancreatitis--personal experience]. 1268 39

Chronic pancreatitis is an inflammatory disease characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. The most frequent causes are alcohol overconsumption and anatomic variants such as pancreas divisum, cholelithiasis, and individual genetic predisposition. The process of fibrosis with consecutive loss of pancreatic parenchyma leads to exocrine insufficiency and maldigestion and, in advanced stages of the disease, to diabetes mellitus. Beside exocrine and endocrine malfunction, mechanical complications occur such as the formation of pancreatic pseudocysts and duodenal and common bile duct obstruction. About 50% of patients with chronic pancreatitis need surgical intervention due to untreatable chronic pain. As recent investigations suggest that the head of the pancreas triggers the chronic inflammatory process, resection of this inflammatory mass must be regarded as pivotal in any surgical intervention. Radical techniques such as the Whipple procedure are undoubtedly successful regarding pain reduction but, even in its pylorus-preserving variant, associated with high postoperative morbidity due to a large loss of pancreatic parenchyma and the absence of duodenal passage. Thirty years ago, H.G. Beger described for the first time the technique of duodenum-preserving pancreatectomy, which better combines resection of the pancreatic head with low morbidity. Over the years, different variations of the original Beger technique (Frey, Izbicky, Berne modification) have been developed, and the excellent results obtained with these methods underline that organ-sparing techniques should be preferred in the surgical treatment of chronic pancreatitis.
 ...
PMID:[Duodenum-preserving pancreas head resection-an operative technique for retaining the organ in the treatment of chronic pancreatitis]. 1500 27

A modified von Frey filament test and an algesiometer paw pressure test were used to measure mechanical nociceptive withdrawal thresholds of the hind limb of control rats and rats injected with streptozotocin (STZ, 50 mg/kg). STZ treatment induced hyperglycemia (HG rats) in about 40% of treated animals. The rest of the STZ-treated and control rats remained normoglycemic (NG rats) throughout the entire experiment. No indications of mechanical hyperalgesia were observed in control groups of animals injected with physiological buffer only. However, both the behavioral tests used detected a 15-30% decrease in the mechanical nociceptive threshold of rats treated with STZ. Furthermore, mechanical nociceptive threshold changes were statistically indistinguishable between NG and HG rats. Glucose tolerance test did not reveal abnormalities of glucose metabolism in NG rats (compared to control animals). However, 1 week after STZ injection, the serum insulin level of NG rats was significantly lower than that of age-matched control rats (0.81 +/- 0.16 vs. 3.5 +/- 0.4 ng/mL; p < 0.01). These data strongly argue that systemic hyperglycemia is not the only factor triggering the development of mechanical hyperalgesia in the STZ rat model of diabetes. Other than hyperglycemia, consequences of insulinemia or insulinemia itself may play an important role in early impairment of mechanical nociception in this animal model.
 ...
PMID:Relevance of hyperglycemia to early mechanical hyperalgesia in streptozotocin-induced diabetes. 1510 93

Diabetic neuropathic pain is one of the most commonly encountered neuropathic pain syndromes. However, the treatment of diabetic neuropathic pain is challenging because of partial effectiveness of currently available pain relievers. It is well known that diabetic animals are less sensitive to the analgesic effect of morphine, and opioids are found to be ineffective in the treatment of diabetic neuropathic pain. Cannabinoids are promising drugs and they share a similar pharmacological properties with opioids. It has been reported that cannabinoid analgesia remained intact and to be effective in some models of nerve injury. Thus, we investigated antinociceptive efficacy and the effects of cannabinoids on behavioral sign of diabetic neuropathic pain in diabetic mice by using WIN 55, 212-2, a cannabinoid receptor agonist. Diabetes was induced by streptozotocin (STZ) (200mg/kg) and animals were tested between 45 and 60 days after onset of diabetes. Antinociception was assessed using the radiant tail-flick test. Mechanical and thermal sensitivities were measured by Von Frey filaments and hot-plate test, respectively. Tactile allodynia, but not thermal hyperalgesia developed in diabetic mice. Systemic WIN 55, 212-2 (1, 5 and 10mg/kg) produced a dose-dependent antinociception both in diabetic and control mice. WIN 55, 212-2-induced antinociception were found to be similar in diabetic mice when compared to controls suggesting efficacy of cannabinoid antinociception was not diminished in diabetic mice. WIN 55, 212-2 also produced a dose-dependent antiallodynic effect in diabetic mice. This study suggests that cannabinoids have a potential beneficial effect on experimental diabetic neuropathic pain.
 ...
PMID:Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect. 1534 39

The antinociceptive action of cannabinoids in acute and inflammatory pain states have been well-documented. There is also accumulating evidence suggesting that cannabinoids are effective analgesics in chronic pain conditions. WIN 55,212-2, a mixed CB1 and CB2 cannabinoid receptor agonist, has been shown to be effective against hyperalgesia and allodynia in painful peripheral mononeuropathy. Recently, in addition to their spinal and supraspinal antinociceptive action, cannabinoids have also reported to exert local analgesic effects. The aim of this study is to observe the effect of a high affinity cannabinoid, WIN 55,212-2, on tactile allodynia and thermal hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindlimbs. Mechanical allodynia was detected by application of von Frey filaments to the plantar surface of the foot, and thermal hyperalgesia was studied using the Hargreaves' method; however, thermal hyperalgesia did not develop in diabetic rats. With its higher doses, both systemic (3 and 10 mg/kg, i.p.) and peripheral (30 microg, i.p.l.) injections of WIN 55,212-2 reduced mechanical allodynia. These results suggest that WIN 55,212-2 has an antiallodynic effect in streptozocin-induced diabetic rats and may be a promising approach in the treatment of diabetic neuropathy.
 ...
PMID:The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. 1551 50

The etiology of painful diabetic neuropathy is poorly understood, but may result from neuronal hyperexcitability secondary to alterations of Ca2+ signaling in sensory neurons. The naturally occurring amino acid taurine functions as an osmolyte, antioxidant, Ca2+ modulator, inhibitory neurotransmitter, and analgesic such that its depletion in diabetes may predispose one to neuronal hyperexcitability and pain. This study reports the effects of taurine replacement on hyperalgesia and sensory neuron Ca2+ homeostasis in streptozotocin-diabetic (STZ-D) rats. Nondiabetic and STZ-D rats were treated with a 2% taurine-supplemented diet for 6-12 wk. Thermal hyperalgesia and mechanical allodynia were determined by measuring hindpaw withdrawal latency to radiant heat and the withdrawal threshold to the von Frey anesthesiometer. Intracellular Ca2+ signaling was explored in neurons from L4-L6 dorsal root ganglia (DRG), using fura 2 fluorescence. Taurine replacement of diabetic rats attenuated deficits of nerve conduction and prevented reductions of mechanical and thermal withdrawal threshold and latency, respectively. In small DRG sensory neurons from diabetic rats, recovery of intracellular Ca2+ concentration ([Ca2+]i) in response to KCl was slowed and 73% corrected by taurine. The amplitudes of caffeine and ATP-induced [Ca2+]i transients were decreased by 47 and 27% (P < 0.05), respectively, in diabetic rat DRG sensory neurons and corrected by 74 and 93% (P < 0.05), respectively, by taurine replacement. These data indicate that taurine is important in the regulation of neuronal Ca2+ signaling and that taurine deficiency may predispose one to nerve hyperexcitability and pain, complicating diabetes.
 ...
PMID:Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats. 1558

Chronic pancreatitis is an inflammatory disease which is characterized by a progressive conversion of pancreatic parenchyma into fibrous tissue. Most frequent causes are alcohol over-consumption, beside anatomic variants such as pancreas divisum, cholelithiasis or individual genetic predisposition. The process of fibrotic transformation with consecutive loss of pancreatic parenchyma leads to exocrine insufficiency and maldigestion, and in advanced stage of the disease to diabetes mellitus. In addition to exocrine and endocrine malfunction, mechanical complications such as formation of pancreatic pseudocysts, duodenal and common bile duct obstruction occur. About 50% of the patients with chronic pancreatitis will need surgical intervention due to intractable chronic pain. Recent investigations suggest that the head of the pancreas triggers the chronic inflammatory process. Therefore, resection of this inflammatory mass must be regarded as the pivotal part of any surgical intervention. Radical techniques such as Whipple-procedure are undoubtedly successful regarding pain reduction. However, even in its pylorus preserving variant this technique is associated with a high postoperative morbidity due to large loss of pancreatic parenchyma and the loss of the duodenal passage. 30 years ago, H. G. Beger described for the first time the technique of duodenum preserving pancreatic head resection that better combines resection of the pancreatic head with low morbidity. Over the years different variations of the original Beger technique (Frey, Izbicky, Berne modification) have been developed, and the excellent results obtained with these techniques underline, that organ sparing procedures should be preferred in the surgical treatment of chronic pancreatitis.
 ...
PMID:Duodenum preserving pancreatic head resection in the treatment of chronic pancreatitis. 1563 14


<< Previous 1 2 3 4 5 6 7 8 Next >>