Mol Pain
-
Oxaliplatin-induced chronic painful neuropathy is the most common dose-limiting adverse event that negatively affects cancer patients' quality of life. However, the underlying molecular mechanisms are still unclear. In the present study, we found that the intraperitoneal administration of oxaliplatin at 4 mg/kg for five consecutive days noticeably upregulated the expression of CXC motif ligand 12 (CXCL12) in the dorsal root ganglion, and the intrathecal injection of an anti-CXCL12 neutralizing antibody or CXCL12 siRNA attenuated the mechanical allodynia and thermal hyperalgesia induced by oxaliplatin. ⋯ Furthermore, the results of a chromatin immunoprecipitation assay revealed that p-STAT3 might be essential for oxaliplatin-induced CXCL12 upregulation via binding directly to the specific position of the CXCL12 gene promoter. Finally, we found that cytokine TNF-α and IL-1β increases mediated the STAT3 activation following oxaliplatin treatment. Taken together, these findings suggested that the upregulation of CXCL12 via TNF-α/IL-1β-dependent STAT3 activation contributes to oxaliplatin-induced chronic pain.
-
Cervical radiculopathic pain is a very common symptom that may occur with cervical spondylosis. Mechanical allodynia is often associated with cervical radiculopathic pain and is inadequately treated with current therapies. However, the precise mechanisms underlying cervical radiculopathic pain-associated mechanical allodynia have remained elusive. ⋯ This increased Ih was supported by the enhanced expression of hyperpolarization-activated, cyclic nucleotide-modulated channels subunit 3 in large dorsal root ganglion neurons. Blockade of Ih with selective antagonist, ZD7288 was able to eliminate the mechanical allodynia associated with cervical radiculopathic pain. This study sheds new light on the functional plasticity of a specific subset of large-diameter dorsal root ganglion neurons and reveals a novel mechanism that could underlie the mechanical allodynia associated with cervical radiculopathy.
-
Acute postoperative pain is induced by most incisional surgeries and usually resolves with wound repair. However, many patients experience moderate to severe pain despite receiving currently available postoperative pain relief. Accumulating evidence suggests that inflammatory cells, neutrophils, and macrophages infiltrating the wound site contribute to the acute inflammation, pain, and subsequent wound repair. Colchicine is commonly used to relieve pain in gout by inhibiting the infiltration of granulocytes and other motile cells. In this study, we examined the effects of colchicine on acute postoperative pain and wound repair by correlating the infiltration of neutrophils and macrophages in a mouse model of postoperative pain induced by plantar incision. Furthermore, these effects of colchicine were compared with clodronate liposomes, which selectively deplete circulating macrophages. ⋯ These results suggest that colchicine can alleviate acute postoperative pain and also enhance the risk of delayed wound repair, which are associated with the suppression of neutrophil and subsequent proinflammatory M1 macrophage infiltration around the incision site, while the involvement of macrophages may be limited.
-
Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. ⋯ Moreover, it was found that the NMDA-induced increase in p-ERK was primarily colocalized with Shank2 proteins in the spinal cord dorsal horn. Conclusion Shank2 protein is involved in spinal NMDA receptor-mediated pain, and mutations of Shank2 may suppress NMDA-ERK signaling in spinal pain transmission. This study provides new clues into the mechanisms underlying pain deficits associated with SIB and deserves further study in patients with ASD.
-
Randomized Controlled Trial
Interaction of acupuncture treatment and manipulation laterality modulated by the default mode network.
Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). ⋯ This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal lobule, inferior parietal lobule, precuneus, and left posterior cingulate cortex. It is also proved that disruptions of the default mode network may account for the cognitive and behavioral impairments in chronic pain patients. Our findings further suggested that default mode network participates in the modulation of spatial-oriented attention on placebo analgesia as a mechanism underlying the degree to which treatment side corresponding to the pain.