Neuropathic pain represents a serious complication arising from a spectrum of disorders that precipitate lesions within the central and peripheral nervous systems. This disabling pain can persist for years, severely diminishing the quality of life of the affected individuals. The treatment options available for neuropathic pain at present have limited efficacy. Moreover, the adverse effects associated with these options restrict their application. The exact etiological mechanisms underlying the pathogenesis of neuropathic pain remain unclear. However, neuroinflammatory processes mediated by the immune system play significant roles in the initiation and progression of neuropathic pain in various models. The nucleotide-binding domain and leucine-rich repeat pyrin-containing protein-3 (NLRP3) inflammasome, a pivotal element of the innate immune system, plays an indispensable role in the pathophysiological mechanisms of central and peripheral neuropathic pain. However, the precise mechanisms facilitating its activation in disparate neuropathic pain conditions remain to be elucidated. Gaining insights into the regulatory mechanisms affecting NLRP3 inflammasome activation in diverse neuropathic pain-associated disorders will aid in developing novel therapeutic avenues. Therefore, this review summarizes the current knowledge on the role of the NLRP3 inflammasome in the pathophysiology of several neuropathic pain-related conditions, such as diabetic neuropathic pain, chemotherapy-induced neuropathic pain, peripheral nerve compression, central nervous system neuropathic pain, radiculopathy, and morphine analgesic tolerance. In addition, this review also discusses the possible use of this inflammasome as a therapeutic target to alleviate the pain-related symptoms of these diseases.

OBJECTIVE: Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life. To assess the role of parabens in this phenomenon, the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province, Iran. METHODS: Adjacent normal-malignant breast tissue samples were obtained from 53 subjects. The parabens including methyl-paraben (MePB), ethyl-paraben (EtPB), propyl-paraben (PrPB), and butylparaben (BuPB) were extracted from the sample supernatant and then subjected to gas chromatography analysis. RESULTS: Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer. We observed a significant association for dose-response pattern of MePB [OR = 98.34 (11.43-185.2), P = 0.027] for both ER+ and PR+ women and MePB [OR = 164.3 (CI: 112.3-216.3), P < 0.001] for HER2+ women than women with negative receptors. The risk of 95-fold increase in MePB dose and 164-fold increase in ΣPBs dose were significant for women with hereditary breast cancer in first-degree relatives. CONCLUSION These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

OBJECTIVETo determine the effects of water hardness on the toxicities of cobalt (Co) and nickel (Ni) to a freshwater fish, Capoeta fusca.

METHODSToxicity was investigated by static bioassay. Fish were exposed to cobalt (as CoCl(2)) and nickel (as NiCl(2)) for 96 h in waters with two levels of hardness ("hard" and "very hard", nominally 130 mg/L and 350 mg/L as CaCO(3), respectively).

RESULTSWater hardness had a significant effect on the acute toxicity of both elements. The 96 h LC(50) values for Co were 91.7 mg/L and 204.8 mg/L in hard and very hard waters, respectively, and for Ni the 96 h LC(50) values were 78.0 mg/L and 127.2 mg/L, respectively.

CONCLUSIONThe fish were more sensitive to Co and Ni toxicity in hard water than in very hard water; very hard water protects C. fusca against the toxicity of Co and Ni.

Animals ; Calcium Carbonate ; analysis ; Cobalt ; analysis ; toxicity ; Cyprinidae ; growth & development ; Environmental Monitoring ; Fresh Water ; analysis ; Iran ; Lethal Dose 50 ; Nickel ; analysis ; toxicity ; Toxicity Tests, Acute ; Water Pollutants, Chemical ; analysis ; toxicity