preproenkephalin and Arthralgia

Joint pain is a major clinical problem mainly associated to osteoarthritis, and characterized by articular cartilage degradation resulting in a complex chronic pain state that includes nociceptive, emotional and cognitive manifestations. Memory impairment, depressive- and anxiety-like symptoms have been reported to be associated with chronic pain, leading to a decrease of life quality. In this study, we evaluated the involvement of the endogenous dynorphin/kappa opioid receptor (KOR) system on the nociceptive, emotional, cognitive, neurochemical and epigenetic manifestations of joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for KOR (KOR-KO), prodynorphin (PDYN-KO) and their wild-type (WT) littermates. KOR-KO and PDYN-KO mice developed mechanical allodynia after intra-articular injection of MIA. This allodynia was significantly increased in both KOR-KO and PDYN-KO when compared to WT mice. Accordingly, both mutants showed increased microglial activation on the lumbar section of the spinal cord after MIA. The emotional responses were evaluated by measuring anxiety-like behaviour in the elevated plus maze and anhedonia as depressive-like behaviour, and cognitive alterations in the object recognition paradigm. Emotional and cognitive impairments after joint pain were differently modified in KOR-KO and PDYN-KO mice. Alterations of corticotropin-releasing factor (CRF) on the amygdala and hippocampus and down regulation of histone 3 acetylation on the amygdala suggest a possible mechanism to explain these emotional and cognitive manifestations. Our results reveal a specific involvement of the dynorphin/KOR system on joint pain manifestations that are usually associated to osteoarthritis.

Topics: Acetylation; Amygdala; Animals; Arthralgia; Chronic Pain; Cognition; Corticotropin-Releasing Hormone; Disease Models, Animal; Emotions; Enkephalins; Epigenesis, Genetic; Hippocampus; Histones; Hyperalgesia; Mice, Inbred C57BL; Mice, Knockout; Microglia; Osteoarthritis; Protein Precursors; Receptors, Opioid, kappa; Spinal Cord

To observe the influence of different moxibustion durations on hypothalamic pro-opiomelanocortin (POMC) and prodynorphin (PDYN) mRNA expressions and plasma beta-endorphin (beta-EP) content in rheumatoid arthritis (RA) rats, to understand the mechanism of moxibustion analgesia and its dose-effect relationship.. Twelve male Wistar rats were randomly selected from 48 male Wistar rats as a normal control group. The RA model was created by raising rats in a windy (blowing with electric fan), cold (6 degrees C +/- 2 degrees C), and wet (80%-90% humidity) environment for 20 days, 12 h each day. This was followed by injection of Freund's complete adjuvant (0.15 mL) into the ankle. Then, rats were randomly divided into a model group, moxibustion group I, and moxibustion group II, with 12 rats in each group. In moxibustion groups I and II, moxibustion was given at Shenshu (BL 23) and Zusanli (ST 36) for 20 and 40 min, respectively, once daily for 15 days. Hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content were determined.. Compared with the normal group, the pressure pain threshold decreased, while the hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content increased in the moxibustion groups (P < 0.01). Compared with the model group, the pressure pain threshold, hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in the moxibustion groups increased significantly (P < 0.01). Compared the moxibustion group I, the pain threshold, hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in moxibustion group II significantly increased (P < 0.01).. Moxibustion has an analgesic effect and increases hypothalamic POMC and PDYN mRNA expression levels and plasma beta-EP content in RA rats.The analgesic effect in moxibustion group II is betterthan that in moxibustion group I.

Topics: Acupuncture Points; Analgesia; Animals; Arthralgia; Arthritis, Rheumatoid; beta-Endorphin; Disease Models, Animal; Enkephalins; Humans; Hypothalamus; Male; Moxibustion; Pain Threshold; Pro-Opiomelanocortin; Protein Precursors; Rats; Rats, Wistar