Articles: hyperalgesia.
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NrCAM, a neuronal cell adhesion molecule in the L1 family of the immunoglobulin superfamily, is subjected to extensively alternative splicing and involved in neural development and some disorders. The aim of this study was to explore the role of Nrcam mRNA alternative splicing in neuropathic pain. A next generation RNA sequencing analysis of dorsal root ganglions (DRGs) showed the differential expression of two splicing variants of Nrcam, Nrcam+10 and Nrcam-10, in the injured DRG after the fourth lumbar spinal nerve ligation (SNL) in mice. ⋯ Nrcam ASO also relieved SNL- or chronic compression of DRG (CCD)-induced the maintenance of pain hypersensitivities in male and female mice. PERSPECTIVE: We conclude that the relative levels of alternatively spliced Nrcam variants are critical for neuropathic pain genesis. Targeting Nrcam alternative splicing via the antisense oligonucleotides may be a new potential avenue in neuropathic pain management.
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Upon transient musculoskeletal diseases, some patients develop persistent pain while others recover from pain. Here, we studied whether such heterogeneity also occurs in rats after recovery from unilateral antigen-induced arthritis (AIA) in the knee joint, and which pain phenotype may predict the course of pain. Typically, inflammatory swelling lasts about 3 weeks. ⋯ However, none of the rats showed an expression of ATF3 in dorsal root ganglion neurons, nor morphological spinal microglia activation thus not suggesting development of neuropathic pain. Both clusters showed a persistent upregulation of pCREB in dorsal root ganglion neurons, inversely correlated with mechanical hyperalgesia at the knee. The role of pCREB needs to be further explored.
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Transcutaneous electrical nerve stimulation (TENS) promotes antinociception by activating the descending pain modulation pathway and consequently releasing endogenous analgesic substances. In addition, recent studies have shown that the endocannabinoid system controls pain. Thus, the present study investigated the involvement of the endocannabinoid system in TENS-induced antinociception of cancer pain using a cancer pain model induced by intraplantar (i.pl.) injections of Ehrlich tumor cells in male Swiss mice. ⋯ These results suggest that low- and high-frequency TENS is effective in controlling cancer pain, and the endocannabinoid system is involved in this effect at both the peripheral and central levels. PERSPECTIVE: TENS is a nonpharmacological strategy that may be used to control cancer pain. Identification of a new mechanism involved in its analgesic effect could lead to the development of clinical studies as well as an increase in its application, lessening the need for pharmacological treatments.
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Breast Cancer Res. Treat. · Jul 2020
Sensory profiles in women with neuropathic pain after breast cancer surgery.
We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). ⋯ Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.
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Neurochemical research · Jul 2020
High Estrogen Level Modifies Postoperative Hyperalgesia via GPR30 and MMP-9 in Dorsal Root Ganglia Neurons.
The cycling of sex hormones is one of the factors affecting pain in females, and the mechanisms are not fully understood. G-protein coupled estrogen receptor 30 (GPR30) is the estrogen receptor known to be involved in mechanical hyperalgesia. Studies have demonstrated that matrix metalloproteinase-9 (MMP-9) is a critical component in peripheral/central nervous system hypersensitivity and neuroinflammation, both of which participate in hyperalgesia. ⋯ In high estrogen level rats with plantar incisions, intrathecal injection of GPR30 antagonist G15 significantly attenuated postoperative hyperalgesia. Intraperitoneal injection of N-acetyl-cysteine, a source of cysteine that prevents the oxidation of cysteine residues on MMP-9, significantly relieved high estrogen-induced postoperative hyperalgesia via suppression of MMP-9 and IL-1β activation in DRGs. These results demonstrate that high estrogen level in rats with incisions elicit GPR30 and MMP-9 upregulation in DRGs and subsequently activate IL-1β, leading to induced postoperative hyperalgesia.