Mitochondria contain respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce a main part of cellular energy in the form of ATP. Mitochondrial disorders occur either due to sporadic or inherited mutations of the genes located in the nuclear or mitochondrial DNA or due to other exogenous factors. Although several proteins related with signalling, assembling, transporting, and enzymatic functions can be impaired in mitochondrial disorders, most frequently the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial disorders usually show a chronic and slowly progressive course and present with multiorgan involvement with varying onsets between birth and late adulthood. They represent a diagnostic challenge because of their wide variations in the presentation and the course. The systems frequently affected in mitochondrial disorders are the peripheral nervous system, brain, endocrine system, heart, eyes, ears, guts, kidneys and bone marrow. Although there is actually no specific therapy and cure for mitochondrial disorders, the rapidly increasing understanding of the pathophysiological background of mitochondrial disorders may further facilitate the diagnostic approach and open perspectives to the future and possibly causative therapies.
Adenosine Triphosphate ; Bone Marrow ; Brain ; DNA, Mitochondrial ; Ear ; Electron Transport ; Endocrine System ; Energy Metabolism ; Heart ; Kidney ; Mitochondria ; Mitochondrial Diseases* ; Oxidative Phosphorylation ; Oxygen ; Parturition ; Peripheral Nervous System

Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the majority of cellular energy in the form of ATP. Mitochondrial disorders are either due to sporadic or inherited mutations of genes located in nuclear or mitochondrial DNA or due to other exogenous factors. Although several proteins related with signalling, assembling, transporting, and enzymatic function can be impaired in mitochondrial disorders, most frequently however, the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial disorders usually show a chronic slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. They represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in mitochondrial disorders are peripheral nervous system, brain, endocrine system, heart, eyes, ears, guts, kidney and bone marrow. Although there is no specific therapy and cure for mitochondrial disorders, the rapidly increasing understanding of the pathophysiological background of the disorders may further facilitate the diagnostic approach and open perspectives to, possibly causative therapies in future.
Adenosine Triphosphate ; Bone Marrow ; Brain ; DNA, Mitochondrial ; Ear ; Electron Transport ; Endocrine System ; Energy Metabolism ; Heart ; Kidney ; Mitochondria ; Mitochondrial Diseases* ; Oxidative Phosphorylation ; Oxygen ; Parturition ; Peripheral Nervous System

The purpose of this study was to study the role of neurofilament (NF) mRNA and calpain in NF reduction of acrylamide (ACR) neuropathy. Male Wistar adult rats were injected i.p. every other day with ACR (20 mg/kg·bW or 40 mg/kg·bW) for 8 weeks. NF mRNA expression was detected using RT-PCR and the calpain concentration was determined using western blot analysis. The NF mRNA expression significantly decreased while the level of m-calpain and μ-calpain significantly increased in two ACR-treated rats groups regardless of the ACR dose. The light NF (NF-L) protein expression was significantly correlated with NF-L mRNA expression. Combined with previous data, the concentrations of three NF subunits were negatively correlated with the calpain levels. These findings suggest that NF-L mRNA and calpain mediated the reduction in NF of ACR neuropathy.
Acrylamide ; toxicity ; Animals ; Calpain ; metabolism ; Gene Expression Regulation ; drug effects ; Intermediate Filaments ; genetics ; Male ; Peripheral Nervous System Diseases ; chemically induced ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats

OBJECTIVETo review the literature on the use of brain imaging, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), magnetic resonance spectroscopy (MRS) and voxel-based morphometry (VBM) in investigation of the activity in diverse brain regions that creates and modulates chronic neuropathic pain.

DATA SOURCESEnglish literatures from January 1, 2000 to July 31, 2007 that examined human brain activity in chronic neuropathic pain were accessed through MEDLINE/CD ROM, using PET, fMRI, VBM, MRS and receptor binding.

STUDY SELECTIONPublished articles about the application of fMRI, PET, VBM, MRS and chronic neuropathic pain were selected.

DATA EXTRACTIONData were mainly extracted from 40 representative articles as the research basis.

RESULTSThe PET studies suggested that spontaneous neuropathic pain is associated with changes in thalamic activity. Both PET and fMRI have been used to investigate the substrate of allodynia. The VBM demonstrated that brain structural changes are involved in chronic neuropathic pain, which is not seen in a matched control group. However, the results obtained had a large variety, which may be due to different pain etiology, pain distribution, lesion tomography, symptoms and stimulation procedures.

CONCLUSIONSApplication of the techniques of brain imaging plays a very important role in the study of structural and functional reorganization in patients with neuropathic pain. However, a unique "pain matrix" has not been defined. Future studies should be conducted using a prospective longitudinal research design, which would guarantee the control for many confounding factors.

Brain ; pathology ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Pain ; pathology ; physiopathology ; Peripheral Nervous System Diseases ; pathology ; physiopathology ; Positron-Emission Tomography ; Receptors, Dopamine ; metabolism ; Receptors, Opioid ; metabolism

Peripheral neuropathies occur in lymphoma patients. Causes of neuropathy include chemotherapy, opportunistic infections, and the lymphoma itself. We report a patient with lymphoma whose chief complaint was a sensory loss in the hands and feet. Electrophysiologic studies and sural nerve biopsy showed sensory polyneuropathies. We hypothesize that this neuropathy is associated with lymphoma-related ganglionopathy, and among the possible causes, we suspect that a systemic cause such as a paraneoplastic syndrome is the most likely pathogenic etiology. However, further follow-up will be necessary to see whether sensory symptoms change with lymphoma treatment.
Adult ; Biopsy ; Electrophysiology ; Hodgkin Disease/*complications/*diagnosis ; Human ; Lymphatic Metastasis ; Lymphoma/*metabolism ; Male ; Peripheral Nervous System Diseases/*complications/*pathology ; Sensation Disorders/complications/pathology

Diseases of the peripheral nervous system are the most prevalent in patients with end-stage renal disease (ESRD). Although increased blood levels of lead in ESRD have been reported, the role of lead remains to be elucidated. The purpose of this study was to determine the connection of blood lead concentration with peripheral nerve conduction velocity. One hundred ninety-eight healthy subjects (control group) and 68 patients with ESRD undergoing hemodialysis (ESRD group) were enrolled. Nerve conduction was measured within two hours after hemodialysis. Orthodromic sensory nerve action potentials and compound muscle action potentials were recorded on the median, ulnar, and radial nerves. Hemoglobin-corrected blood lead was significantly higher in ESRD patients than in controls (9.1+/-2.8 microgram/dL vs. 5.9+/-2.3 microgram/dL, p<0.001). 32.4% of 68 ESRD patients with diabetes mellitus were significantly related to poorer motor and sensory nerve conduction velocity (p<0.001). However, blood lead was not a significant predictor of the nerve conduction velocity (p>0.05). Our result suggested that even though the blood lead levels were high in ESRD, they were not associated with the decline of peripheral nerve function. Diabetes mellitus is a primary independent risk of neuropathy in ESRD patients.
Peripheral Nervous System Diseases/blood/etiology/physiopathology ; Peripheral Nerves/physiopathology ; Neural Conduction/*physiology ; Middle Aged ; Male ; Lead/*blood/metabolism ; Kidney Failure, Chronic/*blood/complications/*physiopathology ; Humans ; Female ; Diabetic Neuropathies/blood/physiopathology ; Case-Control Studies ; Bone and Bones/metabolism ; Body Burden ; Adult

OBJECTIVETo analyze the relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats, and to look for the mechanism of neuropathy and impaired wound healing.

METHODSEighty male SD rats were randomly divided into the normal control group (NC, n = 20), diabetic group (D, n = 20), aminoguanidine-interfered group (AI, n = 20), and insulin-interfered group (II, n = 20) by drawing lots. Diabetes was reproduced in rats of D, AI, and II groups with intraperitoneal injection of streptozotocin (STZ). Then, rats in AI group were fed with 100 mg×kg(-1)×d(-1) aminoguanidine, while rats in II group were subcutaneously injected with insulin for satisfactory control of blood glucose. Changes in mechanical and heat pain thresholds of pad of hind limb were measured at post injection week (PIW) 2, 4, 8. Skin specimens were collected during PIW 2-8 from pads for determination of contents of glucose, advanced glycation end product (AGE), substance P (SP), calcitonin gene-related peptide (CGRP), and observation of distribution and ultrastructure of skin nerve fibers. Data were processed with t test.

RESULTSThe mechanical and heat pain thresholds in D group at PIW 2 [(6.3 ± 1.5) g, (6.0 ± 0.9) s, respectively ] were obviously lower than those in NC group [(13.0 ± 3.2) g, (10.3 ± 1.2) s, with t value respectively 2.71, 3.42, P values all below 0.05]. Contents of glucose and AGE in skin tissue in D group were significantly increased when compared with those in NC group, especially at PIW 8 [(2.85 ± 0.33) mg/g, (31.7 ± 3.2) U/mg of hydroxyproline vs. (0.82 ± 0.22) mg/g, (22.2 ± 1.9) U/mg of hydroxyproline, with t value respectively 1.65, 6.47, P values all below 0.01]. The myelinated nerve fibers were edematous and degenerated, with axons compressed, while the unmyelinated nerve fibers were vacuolated, with microfilament and microtubule disorderly arranged. Content of SP in skin tissue in D group was lower as compared with that in NC group, especially at PIW 2 [(16.8 ± 3.4) pg/g vs. (28.5 ± 5.0) pg/g, t = 2.42, P < 0.01]. There was no obvious difference in content of CGRP between NC and D groups, and also in content of glucose in skin between D and AI groups. Compared with those in D group, content of AGE in AI group at PIW 8 was decreased markedly [(27.2 ± 1.4) U/mg of hydroxyproline, t = 3.38, P < 0.05]; contents of glucose and AGE in II group at PIW 8 were significantly decreased [(1.42 ± 0.38) mg/g, (23.6 ± 1.3) U/mg of hydroxyproline, with t value respectively 1.74, 8.17, P < 0.05 or P < 0.01]. Compared with that in D group, contents of SP in AI and II groups were increased, with a delay in time of trough value. Content of CGRP showed no obvious difference among D, AI, and II groups.

CONCLUSIONSHigh glucose and accumulation of AGE are key mediators of cutaneous neuropathy and impaired wound healing in diabetes mellitus, which confirms that diabetic wound takes an atypical footing during wound repairing. Aminoguanidine and insulin can reduce contents of glucose and AGE in diabetic skin tissue, and ameliorate diabetic cutaneous neuropathy.

Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Glucose ; metabolism ; Glycation End Products, Advanced ; metabolism ; Male ; Peripheral Nervous System Diseases ; etiology ; Rats ; Rats, Sprague-Dawley ; Skin ; metabolism ; pathology ; Skin Diseases ; etiology ; Wound Healing

OBJECTIVETo study the changes in microtubule motor protein expression in the spinal cord and sciatic nerve of rats exposed to carbon disulfide, and to investigate the possible molecular mechanism of changes in axonal transport in carbon disulfide-induced peripheral neuropathy.

METHODSHealthy adult male Wistar rats were randomly divided into one control group and three experimental groups (10 rats per group). The rats in experimental groups were intoxicated by gavage of carbon disulfide at a dose of 200, 400, or 600 mg/kg 6 times a week for 6 consecutive weeks, while the rats in control group were given the same volume of corn oil by gavage. Animals were sacrificed after exposure, with nerve tissue separated. The levels of dynein, dynactin, and kinesin in the spinal cord and sciatic nerve were determined by Western blot.

RESULTSThe content of dynein, dynactin, and kinesin in the sciatic nerve decreased significantly under exposure to carbon disulfide. The levels of dynein in the sciatic nerve were reduced by 23.47% and 33.34% at exposure doses of 400 and 600 mg/kg, respectively. The levels of dynactin in the sciatic nerve of the three experimental groups were reduced by 19.91%, 24.23%, and 41.30%, respectively. The level of kinesin was reduced by 25.98%under exposure to 600 mg/kg carbon disulfide. All the differences were statistically significant (P < 0.01). As compared with the control group, the 600 mg/kg group experienced a 28.24% decrease in level of dynactin in the spinal cord (P < 0.01), but no significant change was observed in the level of dynein or kinesin.

CONCLUSIONCarbon disulfide has an impact on microtubule motor protein expression in nerve tissues, which might be involved in the development of carbon disulfide-induced peripheral neuropathy.

Animals ; Axonal Transport ; drug effects ; physiology ; Carbon Disulfide ; toxicity ; Dynactin Complex ; Male ; Microtubule-Associated Proteins ; metabolism ; Nerve Tissue ; metabolism ; Peripheral Nervous System Diseases ; chemically induced ; metabolism ; Rats, Wistar ; Sciatic Nerve ; metabolism ; Spinal Cord ; metabolism

OBJECTIVETo investigate an effective treatment of peripheral nerve injuries by means of gene transference.

METHODS48 adult Wister rats were divided evenly into 3 groups. A 10 mm sciatic nerve gap was created and bridged with a silicone chamber. The silicone chamber was filled with glial cell-line derived neurotrophic factor(GDNF) gene modified Schwann cells(SCs) (group 1), the normal SCs(group 2) and nothing(the control). At 4, 8, 12, and 16 weeks after the operation, the general and histological observations, the electromyographic and immunohistochemical examinations were performed to the regenerated nerves.

RESULTSThe GDNF-SCs group was significantly better than the SCs and the control groups in nerve conduction velocity, the number and density of reinnervation, the area of regenerated nerve and the thickness of myelin sheath of the regenerated nerves.

CONCLUSIONGDNF gene modified SCs secrete higher levels of neurotrophic factors for a prolonged time, which are more effective in peripheral nerve repair than the normal SCs.

Animals ; Female ; Glial Cell Line-Derived Neurotrophic Factor ; Immunohistochemistry ; Male ; Nerve Growth Factors ; analysis ; genetics ; physiology ; Nerve Regeneration ; physiology ; Peripheral Nerves ; chemistry ; physiopathology ; Peripheral Nervous System Diseases ; surgery ; Rats ; Rats, Wistar ; Schwann Cells ; metabolism ; transplantation

OBJECTIVETo observe the effects and duration of electroacupuncture on the mechanical pain threshold induced by paclitaxel and explore its analgesic mechanism.

METHODSSixty-four C57BL/6J male mice were randomly divided into 4 groups, a normal+sham EA group, a normal+EA group, a medicine+sham EA(Med+ sham EA) group, a medicine + EA (Med + EA) group, 16 cases in each group. The model of chemotherapy-induced peripheral neuropathy was established with paclitaxel intraperitoneal injection on the 1st, 3rd, 5th, 7th day in the Med + sham EA group and the Med + EA group. EA of 30 min was used on bilateral "Zusanli (ST 36)" on the 9th, 11th, 13th, 16th, 18th, 20th, 23rd, 25th, 27th, 30th day in the EA groups, 2 Hz/100 Hz and 1~ 1.5 mA. Acupuncture was applied on the same acupoint at the same times in the sham EA groups. Mechanical pain thresholds were tested by VonFrey before and after model establishment, namely on the 8th, 14th; 21st and, 28th day. The heart blood of 8 mice was drawn quickly to collect serum in every group on the 31st day, and the contents of tumor necrosis factor α (TNF-α), interleukin-1α (IL-1α), interleukin-1β (IL-1β) in proinflammatory cytokine were examined by ELISA. Mechanical pain thresholds were tested by VonFrey for the rest 8 mice of each group until there was no apparent difference in the two paclitaxel groups once a week,namely on the 35th, 42nd, 49th day.

RESULTSThe pain thresholds of each group were not statistically different before model establishment (P > 0.05). After model establishment (on the 8th day), thresholds of the paclitaxel groups were lower than those of the normal groups (all P < 0.05). After EA, the mechanical pain thresholds of the Med + EA group were higher than those of the Med + sham EA group at all the time points, and there was statistical difference on the 14th, 21st and 28th day (all P < 0.05). The analgesic effect was lasting to the 49th day. The contents of TNF-α, IL-1α, IL-1β of the Med + EA group were decreased than those of the Med+sham EA group in different degree, with statistical significance of IL-1α (P < 0.05).

CONCLUSIONEA can effectively treat paclitaxel-induced peripheral neuropathy,and the analgesic mechanism is probably related to decreasing the proinflammatory cytokine.

Acupuncture Points ; Animals ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Electroacupuncture ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasms ; drug therapy ; Peripheral Nervous System Diseases ; etiology ; genetics ; metabolism ; therapy ; Tumor Necrosis Factor-alpha ; genetics ; metabolism