Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of formalin-induced tonic pain (FITP) on testosterone (T) concentrations in the central nervous system (CNS) and serum were investigated in rats. T was nearly eliminated from the brain and spinal cord 1.5 and 24 h after a single subcutaneous injection (100 microl/rat, sc) of 5% formalin and its levels were similar to that seen following castration. In serum, T concentrations were decreased significantly 1.5 h following formalin injection, but after 24 h, the serum level of T was within normal range. T concentrations in the brain, spinal cord, and serum were not modified 20 min after formalin injection. Pretreatment of rats with finasteride, a 5alpha-reductase (5alpha-R) inhibitor (5 mg/kg, sc) blocked T elimination from the brain and spinal cord by FITP, but it failed to prevent decrease in serum T. However, 3 h after administration of exogenous T (5 mg/kg, sc), FITP did not cause a significant decrease in T levels in the CNS and serum. These results suggest that FITP eliminates endogenous T in the brain and spinal cord by increasing 5alpha-R activity in the CNS.
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PMID:Increase in testosterone metabolism in the rat central nervous system by formalin-induced tonic pain. 1237 68

The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals. Male NMRI mice were castrated or sham-operated at the age of 55 days (after puberty). After that, HLDF-6 peptide was injected daily during 3 weeks, followed by behavioral, morphological and biochemical testing. HLDF-6 increased testosterone level (1.5- to 2-fold) both in sham-operated and castrated animals. Sexual activity and pain sensitivity, which are strongly reduced in castrates, were completely or partially recovered by HLDF-6. At the same time, the peptide caused some effects similar to castration in sham-operated animals: aggression and locomotor activity were decreased; oral grooming was prolonged. Morphological studies of accessory sex glands showed that HLDF-6 partially normalizes the morphology and functional activity of seminal vesicles in castrates, but it does not prevent castration-induced apoptosis of prostate epithelial cells. Based on these observations, we can assume that HLDF-6 peptide displays at least two effects on androgen hormones metabolism in males: it stimulates testosterone biosynthesis by both testes and adrenals and simultaneously inhibits its conversion to dihydrotestosterone (DHT), most probably by diminution of 5alpha-reductase isoform 1 mRNA expression.
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PMID:HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice. 1568 Apr 77

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), and sexual dysfunction, are common, highly bothersome conditions in older men, and the prevalence of both disorders increases with age. Sexual dysfunction manifests mainly as erectile dysfunction (ED), ejaculatory disorders, or decreased libido/hypoactive sexual desire (HSD). Whereas both reduced rigidity and reduced ejaculate volume are highly prevalent in ageing men, reduced rigidity and pain on ejaculation are considered to be most bothersome. Sexual dysfunction is much more prevalent in patients with LUTS/BPH than in men with no LUTS/BPH, even after controlling for confounding variables such as age or comorbidities. Hence LUTS/BPH is considered an independent risk factor for sexual dysfunction. Whether this is because of a common underlying pathology, or whether the considerable bother associated with LUTS/BPH leads to reduced sexual functioning, remains to be elucidated. Despite a decline in the frequency of sexual intercourse, as well as in overall sexual functioning, most ageing men report regular sexual activity and consider their sex life as an important dimension of their quality of life (QoL). However, most patients with LUTS/BPH experience a negative effect of their LUTS on their sex life. Hence, treatment of LUTS/BPH should aim to at least maintain or, if possible, improve sexual function. Current medical treatment of LUTS/BPH consists of monotherapy with alpha1-adrenoceptor (AR) antagonists, 5alpha-reductase inhibitors (RIs) or a combination of these. Whereas 5alpha-RIs increase the risk of ED, ejaculatory disorders and HSD, alpha1-AR antagonists can induce ejaculatory disorders, but do not provoke HSD or ED. Combined therapy carries the cumulative risk for sexual dysfunction associated with either type of drug. As already indicated, ED is generally perceived as more bothersome than ejaculatory disorders. In addition, alpha1-AR antagonists slightly improve overall sexual function, possibly by increasing blood flow in the penis through alpha1-AR blockade and/or to an increased overall QoL from the relief of LUTS. It can be concluded that alpha1-AR antagonists constitute a first-line therapy for LUTS/BPH because they combine good treatment efficacy with very few adverse effects on sexual function.
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PMID:Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: sexual function. 1587 31

It has recently been demonstrated that the spinal cord (SC) is an active production center of neuroactive steroids including pregnenolone, dehydroepiandrosterone, progesterone and allopregnanolone. Indeed, anatomical, cellular and biochemical investigations have shown that the SC dorsal horn (DH), a pivotal structure in nociception, contains various active steroidogenic enzymes such as cytochrome P450side-chain-cleavage, cytochrome P450c17, 3beta-hydroxysteroid dehydrogenase, 5alpha-reductase and 3alpha-hydroxysteroid oxido-reductase. Reviewed here are several data obtained with in vitro and vivo experiments showing that endogenous steroids synthesized in the SC are involved in the modulation of nociceptive mechanisms. Various approaches were used as the real-time polymerase chain reaction after reverse transcription to determine the effects of neuropathic pain on the expression of genes encoding steroidogenic enzymes in the DH. Combination of the pulse-chase technique with high performance liquid chromatography and continuous flow scintillation detection allowed investigations of the impact of noxious signals on the activity of steroid-producing enzymes in the SC in vitro. Radioimmunological analyses of spinal tissue extracts contributed to determine the link between the painful state and endogenous steroid secretion in the SC in vivo. Finally, the physiological relevance of the modification of endogenous steroid formation in the SC during painful situation was discussed.
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PMID:Endogenous steroid production in the spinal cord and potential involvement in neuropathic pain modulation. 1843 33

Finasteride is a potent drug which has been prescribed for the management of benign prostatic hyperplasia (BPH) for more than 20 years. Recent studies indicate that finasteride, as 5alpha-reductase inhibitor, can influence some central effects such as analgesia, neurosteroidogeneses and behavior. The purpose of this study was to investigate the analgesic effect of finasteride, to determine whether finasteride interact with morphine analgesia in tail-flick test and to examine the anti-inflammatory effect of this drug. Adult male Wistar rats (280-330 g) were used for the both of experiments. Tests were assessed on groups of 6 animals. The first control group (O) received water (1 ml/kg, p.o.), the second control group (OO) received the vehicle (olive oil, 1 ml/kg, p.o.) and the third group (F) received finasteride (0.5 mg/kg, p.o.) suspended in olive oil, every morning for 30 days. After 30 days of treatment, tail-flick test and formalin-induced foot paw edema test were performed. Finasteride increased the average latency in seconds in comparison to both controls (10.06 vs. 9.16 and 8.66 s). It was 9.83% higher depression of pain in group F in comparison to O and 16.17% in comparison to OO, but the anti-nociceptive effect of finasteride at applied dose didn't significantly differ compared to both controls (p > 0.05). Chronic pre-treatment with finasteride didn't interact with analgesic effect of morphine compared to O (p > 0.05), but compared to OO finasteride fastened, increased and prolonged the analgesic effect of morphine at all measuring intervals, achiving statistical significance in 60 min (p < 0.01). Finasteride also exhibited significant anti-inflammatory action (p < 0.05) in comparison to OO, but It was not significantly different from the control O. Finasteride didn't exert analgesic action, it increased morphine antinociception and showed chronic anti-inflammatory effect to some extent. This might be a useful contribution to highlight the pathogenesis of BPH. There is the need for further studies in order to confirm these results with more details.
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PMID:Anti-nociceptive and anti-inflammatory properties of 5alpha-reductase inhibitor finasteride in experimental animals. 1900 44

The National Institutes of Health (NIH) has redefined prostatitis into four distinct entities. Category I is acute bacterial prostatitis. It is an acute prostatic infection with a uropathogen, often with systemic symptoms of fever, chills and hypotension. The treatment hinges on antimicrobials and drainage of the bladder because the inflamed prostate may block urinary flow. Category II prostatitis is called chronic bacterial prostatitis. It is characterized by recurrent episodes of documented urinary tract infections with the same uropathogen and causes pelvic pain, urinary symptoms and ejaculatory pain. It is diagnosed by means of localization cultures that are 90% accurate in localizing the source of recurrent infections within the lower urinary tract. Asymptomatic inflammatory prostatitis comprises NIH category IV. This entity is, by definition, asymptomatic and is often diagnosed incidentally during the evaluation of infertility or prostate cancer. The clinical significance of category IV prostatitis is unknown and it is often left untreated. Category III prostatitis is called chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). It is characterized by pelvic pain for more than 3 of the previous 6 months, urinary symptoms and painful ejaculation, without documented urinary tract infections from uropathogens. The syndrome can be devastating, affecting 10-15% of the male population, and results in nearly 2 million outpatient visits each year. The aetiology of CP/CPPS is poorly understood, but may be the result of an infectious or inflammatory initiator that results in neurological injury and eventually results in pelvic floor dysfunction in the form of increased pelvic muscle tone. The diagnosis relies on separating this entity from chronic bacterial prostatitis. If there is no history of documented urinary tract infections with a urinary tract pathogen, then cultures should be taken when patients are symptomatic. Prostatic localization cultures, called the Meares-Stamey 4 glass test, would identify the prostate as the source for a urinary tract infection in chronic bacterial prostatitis. If there is no infection, then the patient is likely to have CP/CPPS. For healthcare providers, the focus of therapy is symptomatic relief. The first therapeutic measure is often a 4- to 6-week course of a fluoroquinolone, which provides relief in 50% of men and is more efficacious if prescribed soon after symptoms begin. Second-line pharmacotherapy involves anti-inflammatory agents for pain symptoms and alpha-adrenergic receptor antagonists (alpha-blockers) for urinary symptoms. Potentially more effective is pelvic floor training/biofeedback, but randomized controlled trials are needed to confirm this. Third-line agents include 5alpha-reductase inhibitors, glycosaminoglycans, quercetin, cernilton (CN-009) and saw palmetto. For treatment refractory patients, surgical interventions can be offered. Transurethral microwave therapy to ablate prostatic tissue has shown some promise. The treatment algorithm provided in this review involves a 4- to 6-week course of antibacterials, which may be repeated if the initial course provides relief. Pain and urinary symptoms can be ameliorated with anti-inflammatories and alpha-blockers. If the relief is not significant, then patients should be referred for biofeedback. Minimally invasive surgical options should be reserved for treatment-refractory patients.
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PMID:Chronic prostatitis: management strategies. 1919 37

Dorsal root ganglia (DRG) which contain glial cells and somas of primary sensory neurons are pivotal for neural transmission between the peripheral and central nervous systems. It is well established that neuropeptides such as substance P and calcitonin gene-related peptide located in DRG neurons control sensory and pain mechanisms. However, contrary to the brain and spinal cord which are extensively investigated, DRG received little attention. Therefore, the current knowledge on DRG may be far to represent their complete neurochemical potential. For instance, until 1997, nothing was known on DRG neurosteroidogenic ability but recently, several investigations have shown that DRG contain various key enzymes synthesizing neuroactive neurosteroids. To provide new advances into DRG neurochemistry, we reviewed and highlighted herein basic and functional evidence showing that neurosteroids are produced in DRG through a neuron-glia crosstalk mechanism. Indeed, key enzymes producing neurosteroids including pregnenolone, progesterone, dihydroprogesterone and estradiol are differentially expressed in DRG cell types. Cytochrome P450side-chain-cleavage is located in DRG neurons and satellite glial cells, 3beta-hydroxysteroid dehydrogenase is expressed in Schwann cells and neurons, 5alpha-reductase is localized in satellite glial and Schwann cells (not in neurons) while aromatase is present in neurons but not in glia. Recent studies also revealed that DRG neurosteroidogenesis is a physiologically relevant process selectively regulated under pathological conditions. Acting through paracrine and autocrine mechanisms, endogenous neurosteroids modulate DRG sensory functions and protect DRG neurons against death. The paper suggests that DRG neurosteroidogenic components may be targeted for the development of therapies against peripheral nerve injury-induced afferent noxious stimulations.
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PMID:Progress in dorsal root ganglion neurosteroidogenic activity: basic evidence and pathophysiological correlation. 2043 98