Articles: hyperalgesia.
-
Chronic widespread pain is a serious medical problem, yet the mechanisms of nociception and pain are poorly understood. Using a reserpine-induced pain model originally reported as a putative animal model for fibromyalgia, this study was undertaken to examine the following: (1) expression of several ion channels responsible for pain, mechanotransduction, and generation/propagation of action potentials in the dorsal root ganglion (DRG), (2) activities of peripheral nociceptive afferents, and (3) alterations in spinal microglial cells. A significant increase in mRNA expression of the acid-sensing ion channel (ASIC)-3 was detected in the DRG, and the behavioral mechanical hyperalgesia was significantly reversed by subcutaneous injection of APETx2, a selective blocker of ASIC3. ⋯ The activated microglia and behavioral hyperalgesia were significantly tranquilized by intraperitoneal injection of minocycline. These results suggest that the increase in ASIC3 in the DRG facilitated mechanical response of the remaining C-nociceptors and that activated spinal microglia may direct to intensify pain in this model. Pain may be further amplified by reserpine-induced dysfunction of the descending pain inhibitory system and by the decrease in peripheral drive to this system resulting from a reduced proportion of mechanoresponsive C-nociceptors.
-
In an effort to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two protease-activated receptors, protease-activated receptor 2 (PAR2), and protease-activated receptor 4 (PAR4), in dorsal root ganglia (DRGs) neurons in an animal model of bone cancer pain. Female Wistar rats were randomized into three groups: tumor-bearing animals killed after 14 days (D14) and tumor-bearing animals killed after 21 days (D21) group and a sham operation group. After establishment of the Walker 256 carcinoma bone cancer pain model, behavioral tests were carried out to determine both the spontaneous nocifensive behavior and the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia in these rats. ⋯ Compared to sham group, the relative mRNA and protein expression of PAR2 and PAR4 was significantly upregulated in the D14 group and D21 groups, concurrent with tumor growth and proliferation. In addition, we identified the co-expression of PAR2 and PAR4 in the DRG neurons. The upregulation of mRNA and protein levels as well as the co-localization of PAR2 and PAR4 in DRG neurons suggests their novel involvement in the development and maintenance of bone cancer pain.
-
Hormone replacement remains one of the common therapies for menopause-related pain but is associated with risk of orofacial or back pain. Spinal endomorphin-2 (EM-2) is involved in varied pain and its release is steroid-dependent, but whether increasing spinal EM-2 can inhibit thermal hyperalgesia and inflammatory pain in ovariectomized (OVX) female rats, an animal model mimicking menopause, is not clear, nor is the potential involvement of spinal mu-opioid receptor (MOR). In the current study, we revealed that the temporal decrease of spinal EM-2 is accompanied with OVX-induced thermal hyperalgesia that was dose-dependently attenuated by intrathecal (IT) delivery of EM-2. ⋯ Furthermore, IT delivery of EM-2 did not affect the animals' locomotion or anxiety status. Our findings suggested that IT EM-2 might be a safer analgesia strategy than hormone replacement therapy in reducing risk of orofacial or back pain. However, a long-lasting form of EM-2 with less tolerance is needed to induce sustained analgesia.
-
Neurochemical research · Mar 2015
Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-α, IL-1β and IL-6.
Reactive oxygen species are signaling mediators of nociceptive pathways. Exogenous administrations of antioxidants show anti-hyperalgesic effect. However, very little is known about the role of endogenous antioxidant defense system in pain pathology. ⋯ The changes were brought towards normal level after curcumin treatment. The results suggest that modulation of antioxidant defense system is early event in initiation of inflammatory hyperalgesia which might lead to initiation of other signaling pathways mediated by lipid peroxide, TNF-α, IL-1β and IL-6. Decrease in oxidative stress and down regulation of these cytokines by curcumin is suggested to be involved in its anti-hyperalgesic effect.
-
Cannabinoids produce anti-nociceptive and anti-hyperalgesic effects in acute, inflammatory and neuropathic pain models. The current study investigated the role of cannabinoid (CB1 and CB2) receptors in modulating formalin-induced nociceptive behavior and mechanical allodynia in the rat. Rats received subcutaneous plantar injections of 5% formalin in the hind paws. ⋯ Animals in the experimental group were given i.p. injections of CB1 and CB2 receptor antagonists AM281 and AM630 at a dose of 1 mg/kg concomitant with formalin, and then twice daily for the following 7 days. AM281 and AM630 enhanced nociceptive behaviors, and attenuated the bilateral mechanical paw withdrawal threshold, compared with the vehicle. The results indicate that CB1 and CB2 receptors mediate a tonically inhibitory action on formalin-induced inflammatory pain, especially long-term allodynia, in bilateral hind paws.