Protection of Sensory Function and Antihyperalgesic Properties of a Prosaposin-derived Peptide in Diabetic Rats

2000 ◽  
Vol 93 (5) ◽  
pp. 1271-1278 ◽  
Author(s):  
Nigel A. Calcutt ◽  
Jason D. Freshwater ◽  
John S. O’Brien

Background Short-term diabetes causes sensory disorders in rats ranging from thermal hypoalgesia to exaggerated behavioral responses to other sensory stimuli. As impaired neurotrophic support may promote sensory nerve disorders during diabetes, the authors investigated whether TX14(A), a neurotrophic peptide derived from prosaposin, was able to ameliorate nerve disorders in diabetic rats. Methods TX14(A) was delivered by intraperitoneal or intrathecal injection to control or streptozotocin-diabetic rats in either single or multiple (three times weekly) dose regimens. Efficacy was measured against diabetes-induced disorders of sensory nerve conduction velocity, paw withdrawal latency to radiant heat, tactile response thresholds to von Frey filaments, and flinching after paw formalin injection. Results Prolonged TX14(A) treatment of diabetic rats prevented the progressive decline in large sensory fiber conduction velocity in the sciatic nerve, development of paw thermal hypoalgesia, and increased flinching after paw formalin injection. The effect on formalin hyperalgesia persisted for 48 h but not 72 h after injection. No effects were noted in control rats. A single injection of TX14(A) 30 min before testing did not alter thermal response latencies in control or diabetic rats but prevented formalin hyperalgesia in diabetic rats. Tactile allodynia and the prolonged paw thermal hyperalgesia to radiant heat after intrathecal delivery of substance P were also dose-dependently ameliorated in diabetic rats by a single injection of TX14(A), whereas no effects were observed on the responses to these tests in control rats. Conclusions TX14(A) exhibits both neuroprotective and acute antihyperalgesic properties in diabetic rats without altering normal nociceptive function.

2000 ◽  
Vol 1 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Heather Flint ◽  
Mary A. Cotter ◽  
Norman E. Cameron

Pentoxifylline has several actions that improve blood rheology and tissue perfusion and may therefore potentially be applicable to diabetic neuropathy. The aims of this study were to ascertain whether 2 weeks of treatment with pentoxifylline could correct nerve conduction velocity and blood flow deficits in 6-week streptozotocin-diabetic rats and to examine whether the effects were blocked by co-treatment with the cyclooxygenase inhibitor, flurbiprofen, or the nitric oxide synthase inhibitor,NG-nitro-ʟ-arginine. Diabetic deficits in sciatic motor and saphenous sensory nerve conduction velocity were 56.5% and 69.8% corrected, respectively, with pentoxifylline treatment. Sciatic endoneurial blood flow was approximately halved by diabetes and this deficit was 50.4% corrected by pentoxifylline. Flurbiprofen co-treatment markedly attenuated these actions of pentoxifylline on nerve conduction and blood flow whereasNG-nitro-ʟ-arginine was without effect. Thus, pentoxifylline treatment confers neurovascular benefits in experimental diabetic neuropathy, which are linked at least in part to cyclooxygenasemediated metabolism.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Brian Dake ◽  
Mark A. Yorek

We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.


1998 ◽  
Vol 244 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Noriaki Kato ◽  
Mitsuhiro Makino ◽  
Kuniharu Mizuno ◽  
Tsunemasa Suzuki ◽  
Masaomi Shindo

Diabetes ◽  
1989 ◽  
Vol 38 (6) ◽  
pp. 730-736 ◽  
Author(s):  
R. E. Carsten ◽  
L. R. Whalen ◽  
D. N. Ishii

Author(s):  
Riccardo Marvulli ◽  
Giancarlo Ianieri ◽  
Grazia Devenuto ◽  
Marta Falcicchio ◽  
Giulia A. Gallo ◽  
...  

Background and Objective: Carpal tunnel syndrome (CTS) is the most common form of nerve entrapment. Clinically, various signs and symptoms compare due to overexposure to mechanical vibrations transmitted to the wrist bones and cartilage, resulting in compression of the sensory and motor nerve fibers of median nerve. Early symptoms include nocturnal paresthesia and electromyography reveals reduced sensory nerve conduction velocity. Aim of this study was to evaluate the efficacy of a dietary integrator composed of acetyl-L-carnitine, α-lipoic acid,quercetin, bromelain, pantothenic acid, C and B1 and B2 and B6 and B12 vitamins in patients with early (minimal) carpal tunnel syndrome. Methods: 36 patients (28 female and 8 male) with early CTS characterized by sensory nerve demyelination and inflammation of the transverse carpal ligament. Patients were divided into two groups, group A (18 patients received physical therapy) and group B (18 patients, received physical therapy and an oral integrator). Clinical (sleep quality questionnaire to measure severity of paresthesia) and neurophysiological assessment (Sensory Nerve Conduction Velocity) performed at baseline, and then at 30 and 60 days after treatment. Results: Sleep quality and Sensory Nerve Conduction Velocity data analysis show improvement in both groups at 30 and 60 days, with statistically difference between them in both time of analysis. Conclusions: In the early CTS, with sensory fibers damage, use of dietary integrator, such as Micronil Dol®, composed composed of acetyl-L-carnitine, α-lipoic acid,quercetin, bromelain, pantothenic acid, C and B1 and B2 and B6 and B12 vitamins can be effective in quick recovery of median nerve sensory.


2021 ◽  
Vol 9 (1) ◽  
pp. e001698
Author(s):  
Haifa Maalmi ◽  
Kristiaan Wouters ◽  
Hans H C M Savelberg ◽  
Jeroen H P M van der Velde ◽  
Jos P H Reulen ◽  
...  

IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.


Author(s):  
Abbas Alimoradian ◽  
Fatemeh Samimi ◽  
Hadise Aslfalah ◽  
Seied Amirhossein Latifi ◽  
Mehdi Salehi ◽  
...  

Abstract Objectives Pain associated with various underlying pathologies is a major cause of morbidity and diminished life quality in diabetic patients. Effective control of pain requires the use of analgesics with the best efficacy and with minimal side effects. Therefore, our aim in this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on pain in diabetic rats. Methods In this study, we investigated the analgesic effects of drugs belonging to three different classes of NSAIDs in a rat model of diabetes. Four diabetic groups received normal saline, diclofenac, piroxicam and ketorolac, respectively, and four non-diabetic groups received normal saline, diclofenac, piroxicam and ketorolac. Type 1 diabetes was induced in rats by a single injection of streptozotocin (60 mg/kg bw). Formalin (50 µL of 2.5%) nociception assay was used to examine the effect of treatment with diclofenac, piroxicam and ketorolac on acute and chronic pain in healthy and diabetic rats. Results Piroxicam showed significant analgesic effects both in the acute phase of pain (5–10 min after injection of formalin into the left hind paw), and in the chronic phase (20–60 min after formalin injection) in healthy as well as diabetic rats. Diclofenac and ketorolac also reduced pain scores in healthy rats. However, these two drugs failed to diminish pain in diabetic rats. Conclusion Our data point for better efficacy of piroxicam in controlling pain in diabetes.


2001 ◽  
Vol 95 (2) ◽  
pp. 525-530 ◽  
Author(s):  
Shao-Rui Chen ◽  
Hui-Lin Pan

Background Systemic morphine is known to cause increased release of acetyicholine in the spinal cord. Intrathecal injection of the cholinergic receptor agonists or acetyicholinesterase inhibitors produces antinociception in both animals and humans. In the present study, we explored the functional importance of spinal endogenous acetylcholine in the analgesic action produced by intravenous morphine. Methods Rats were implanted with intravenous and intrathecal catheters. The antinociceptive effect of morphine was determined by the paw-withdrawal latency in response to a radiant heat stimulus after intrathecal treatment with atropine (a muscarinic receptor antagonist), mecamylamine (a nicotinic receptor antagonist), or cholinergic neurotoxins (ethylcholine mustard aziridinium ion [AF64A] and hemicholinium-3). Results Intravenous injection of 2.5 mg/kg morphine increased significantly the paw-withdrawal latency. Intrathecal pretreatment with 30 microg atropine (n = 7) or 50 microg mecamylamine (n = 6) both attenuated significantly the antinociceptive effect of morphine. The inhibitory effect of atropine on the effect of morphine was greater than that of mecamylanilne. Furthermore, the antinociceptive effect of morphine was significantly reduced in rats pretreated with intrathecal AF64A (n = 7) or hemicholinium-3 (n = 6) to inhibit the high-affinity choline transporter and acetylcholine synthesis. We found that intrathecal AF64A reduced significantly the [3H]hemicholinium-3 binding sites but did not affect its affinity in the dorsal spinal cord. Conclusions The data in the current study indicate that spinal endogenous acetylcholine plays an important role in mediating the analgesic effect of systemic morphine through both muscarinic and nicotinic receptors.


1967 ◽  
Vol 46 (1) ◽  
pp. 63-84
Author(s):  
K. M. CHAPMAN ◽  
J. H. PANKHURST

1. Conduction velocities of individual afferent nerve fibres from tactile spines and proprioceptive campaniform sensilla have been measured in situ over the temperature range 5-42° C., in leg preparations of the cockroach Periplaneta americana. 2. Conduction velocities at 20° C. (u20) averaged 3.3±1.4 m./sec., ranging from 1.6 to 11.0 m./sec. 3. Temperature coefficients, expressed as Q10 for the interval 20-30° C., averaged 1.7±0.24, ranging from 1.3 to 2.6. 4. The length of the propagated disturbance is about 2-3 mm., and is nearly temperature-independent. 5. Fibre diameters, estimated from conduction velocity, must be about 10 µ. 6. There is no correlation between conduction velocity and distance from the sensillum to the thoracic ganglion. Conduction delays in fibres conducting within one standard deviation of mean u20 range from about 2 to 15 msec., from the most proximal to the most distal tactile spines. 7. The effect of conduction delay on temporal and spatial sensory encoding is probably unimportant from a behavioural point of view. It contributes a factor of the form exp(-sd/u) to the sensory transfer function, and may be appreciable at upper physiological frequencies of impulse frequency modulation.


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