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

Tricyclic antidepressants rarely cause peripheral neuropathy. In fact, this class of drugs has been used to control the symptoms of pain and paresthesia that accompany peripheral neuropathy. We report peripheral paresthesias that occurred in a 39-year-old female during five years of amitriptyline administration. The patient's symptoms were relieved by oral pyridoxine hydrochloride, associated with elevated plasma pyridoxal phosphate.
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PMID:Amitriptyline-related peripheral neuropathy relieved during pyridoxine hydrochloride administration. 629 93

Mastalgia is a common but often poorly understood condition with little Australian data available on the subject. Details are presented of 170 patients who have attended a specific mastalgia clinic at the Princess Alexandra Hospital, Brisbane, Queensland, over a 3 year period. The aims and management protocol of the clinic are outlined. The mastalgia sufferer in this study had an average age of 42 years and 87% were multiparous. Cyclical pain occurred in 59% as determined by a daily pain record chart. Unilateral pain occurred in 38%. Lack of previous breast feeding and low levels of regular physical exercise were identified as two significant factors in the history of those attending the clinic. The responses to treatments are outlined. Response rates of 18 and 26% to two commonly used 'natural products', Vitamin B6 and Evening Primrose Oil, respectively, are considered little better than placebo effect. A complete response was achieved in 67% of women who took low dose danazol with minimal side effects. The overall response rate to all treatments was 65% with a mean follow up of 15.5 months for those women who continued to attend the clinic. For women with mastalgia, a systematic approach can achieve relief of pain.
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PMID:Mastalgia: a 3 year Australian study. 817 29

The role of vitamin B6 as a therapeutic agent in the treatment of carpal tunnel syndrome was examined by monitoring both the standard clinical and electrophysiological parameters for entrapment neuropathy at the wrist. Electroencephalogram (EEG) studies were done in an attempt to identify patients most likely to benefit from B6 treatment. EEGs did not prove useful as predictors of clinical response to vitamin B6. Our patients, however, did not show any abnormalities prior to treatment, and no changes occurred during the treatment period. Motor latency, while the most common screening test for carpal tunnel syndrome, was not significantly changed during the course of treatment. It did not prove to be a useful test for monitoring clinical effectiveness of the treatment. Parameters showing the greatest changes were pain scores and sensory latency, which most closely paralleled clinical assessments. Pain scores, more than any other parameters, were improved in these patients following vitamin B6 treatment. Vitamin B6 has been shown to change pain thresholds in clinical and laboratory studies. This may be the basis of the significant improvement in pain scores when electrophysiologic data showed only mild improvement. This study suggests that vitamin B6 deficiency may not be a cause of carpal tunnel syndrome in spite of the observed therapeutic effect, without toxicity, of vitamin B6 treatment.
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PMID:Brief communication: effect of pharmacologic doses of vitamin B6 on carpal tunnel syndrome, electroencephalographic results, and pain. 844 Aug 21

Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.
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PMID:High-dose pyridoxine as an 'anti-stress' strategy. 1085 91

Disregarding pain resulting from vitamin deficiency, an analgesic effect seems to be exerted only by vitamin B1 (thiamine), vitamin B6 (pyridoxines), and vitamin B12 (cobalamine), particularly when the three are given in combination. The analgesic effect is attributed to an increased availability and/or effectiveness of noradrenaline and 5-hydroxytryptamine acting as inhibitory transmitters in the nociceptive system. In animal experiments, high doses of these vitamins administered alone or in combination inhibited nociceptive behavior and depressed the nociceptive activity evoked in single neurons of the dorsal horn of the spinal cord and in the thalamus. Moreover, they were found to enhance the antinociceptive effect of non-opioid analgesic agents on withdrawal reflexes. Clinical data fail in most cases to meet current standards of evaluation (randomization, double-blindness). Still, it appears that high doses of the vitamins B1, B6, and B12 administered separately or in combination can alleviate acute pain and potentiate the analgesia caused by non-opioid analgesics such as the NSAIDs and metamizol (dipyrone). Therapeutic effects are observed in neuropathic pain and pain of musculoskeletal origin. Vitamin B6 is effective in the carpal tunnel syndrome which, however, is attributed at least in some cases to vitamin B6 deficiency. It is also worth noting that the B vitamins are shown to enhance the beneficial effect of diclofenac in acute low-back pain so that either the duration of treatment or the daily dose of diclofenac may be reduced. The use of high doses of vitamin B6 may be limited by a neurotoxic effect. The effectiveness of B vitamins in depressing chronic pain has not been established. It would be interesting to know if the B vitamins are of use as adjuvants in the treatment of tumor pain.
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PMID:[Analgesic and analgesia-potentiating action of B vitamins]. 1279 82

Polyneuropathy related to decreased levels of Vitamin B6 are well known. In contrast, the association between elevated levels of pyridoxine and neuropathy is not well described. This study is a retrospective review of patients in our neuromuscular clinic that were found to have elevated B6 levels. Twenty-six patients were found to have elevated serum B6 levels. The mean B6 level was 68.8 ng/ml. Twenty patients (76.9%) reported daily vitamin use. Twenty-one patients (80.8%) reported only sensory complaints. The most common symptoms reported were numbness (96%), burning pain (49.9%), tingling (57.7%), balance difficulties (30.7%), and weakness (7.8%). Nine (out of 26) had an abnormal EMG/NCS. Eight patients had an abnormal quantitative sensory study. We conclude that elevated pyridoxine levels should be considered in the differential diagnosis of any sensory or sensorimotor polyneuropathy.
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PMID:Elevated B6 levels and peripheral neuropathies. 1875 31

Opioids, although fundamental to the treatment of pain, are limited in efficacy by side effects including tolerance and hyperalgesia. Using an in vitro culture system, we report that morphine increased microglial migration via a novel interaction between mu-opioid and P2X(4) receptors, which is dependent upon PI3K/Akt pathway activation. Morphine at 100 nm enhanced migration of primary microglial cells toward adenosine diphosphate by 257, 247, 301, 394, and 345% following 2, 6, 12, 24, and 48 h of stimulation, respectively. This opioid-dependent migration effect was inhibited by naloxone and confirmed to be mu-opioid receptor-dependent through the use of selective agonists and antagonists. PPADS [pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid)], a P2X(1-3,5-7) antagonist, had no effect on microglial migration; however, TNP-ATP [2',3'-O-(2,4,6-trinitrophenyl)-ATP], a P2X(1-7) antagonist, inhibited morphine-induced migration, suggesting a P2X(4) receptor-mediated effect. The PI3K inhibitors wortmannin and LY294002 decreased morphine-induced microglial migration. Iba1 protein, a microglial marker, and P2X(4) receptor expression were significantly increased after 6, 12, 24, and 48 h of morphine stimulation. Together, these results provide evidence for two phases of morphine effects on microglia. The initial phase takes place in minutes, involves PI3K/Akt pathway activation and leads to acutely enhanced migration. The longer-term phase occurs on the order of hours and involves increased expression of Iba1 and P2X(4) receptor protein, which imparts a promigratory phenotype and is correlated with even greater migration. These data provide the first necessary step in supporting microglial migration as an attractive target for the prevention or attenuation of morphine-induced side effects including tolerance and hyperalgesia.
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PMID:Morphine enhances microglial migration through modulation of P2X4 receptor signaling. 1917 8

Increased sensitivity of the afferent innervation of the gastrointestinal tract reportedly underlies symptoms of discomfort and pain in functional bowel disorders. The present investigation aimed to examine whether the purinergic P2X(2) and P2X(3) receptor subunits contribute to the mechanosensitivity of small intestinal afferents in normal mice and in a murine model of postinfectious gut dysfunction. Mesenteric afferent nerve activity was recorded in a mouse jejunum preparation maintained in vitro. As has been shown previously, ramp distension of the jejunal segment evoked biphasic afferent discharge, reflecting activation of low and high threshold fibres. The average pressure-afferent response curve in mice deficient in both P2X(2) and P2X(3) subunits (n = 14) was not significantly different from that of the wild-type control preparations (n = 13). Application of pyridoxal 5-phosphate 6-azophenyl-2 ,4-disulphonic acid (PPADS) (30 micromol L(-1)), a P2X and P2Y antagonist, or 2,4,6-trinitrophenol-adenosine 5'-triphosphate (10 micromol L(-1)), an antagonist selective for homomeric P2X(3) and heteromeric P2X(2/3) receptors, had no effect on the averaged pressure-afferent response curve in wild-type animals. In Trichinella spiralis-infected mice, the magnitude of mesenteric afferent responses to jejunal distension was greater at day 21 and day 56 postinfection compared with the sham control preparations demonstrating the development of afferent hypersensitivity. PPADS had no significant effect upon mechanically evoked afferent discharge rates in sham treated preparations (n = 5), but significantly inhibited afferent sensitivity to jejunal distension in preparations from mice at day 21 (n = 6) and day 56 (n = 7) postinfection. These results suggest that purinergic mechanisms play no role in mechanosensory transduction in the normal small intestine but contribute significantly to postinfectious mechano-hypersensitivity.
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PMID:Purinergic contribution to small intestinal afferent hypersensitivity in a murine model of postinfectious bowel disease. 1922 Jul 57

Vitamin B6 is an essential vitamin needed for many chemical reactions in the human body. It exists as several vitamins forms but pyridoxal 5'-phosphate (PLP) is the phosphorylated form needed for transamination, deamination, and decarboxylation. PLP is important in the production of neurotransmitters, acts as a Schiff base and is essential in the metabolism of homocysteine, a toxic amino acid involved in cardiovascular disease, stroke, thrombotic and Alzheimer's disease. This report announces the connection between a deficit of PLP with a genetically linked physical foot form known as the Morton's foot. Morton's foot has been associated with fibromyalgia/myofascial pain syndrome. Another gene mutation methylenetetrahydrofolate reductase (MTHFr) is now being recognized much commonly than previous with chronic fatigue, chronic Lyme diseases and as "the missing link" in other chronic diseases. PLP deficiency also plays a role in impaired glucose tolerance and may play a much bigger role in the obesity, diabetes, fatty liver and metabolic syndrome. Without the Schiff-base of PLP acting as an electron sink, storing electrons and dispensing them in the mitochondria, free radical damage occurs! The recognition that a phenotypical expression (Morton's foot) of a gene resulting in deficiency of an important cofactor enzyme pyridoxal 5'-phosphate will hopefully alert physicians and nutritionist to these phenomena. Supplementation with PLP, L5-MTHF, B12 and trimethylglycine should be used in those patients with hyperhomocysteinemia and/or MTHFR gene mutation.
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PMID:Morton's foot and pyridoxal 5'-phosphate deficiency: genetically linked traits. 2544 36

Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
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PMID:The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. 2871 55


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