Articles: hyperalgesia.
-
Human experimental pain models provide an important translational link between pre-clinical models and clinical pain. Using topical capsaicin and continuous heat application, the novel capsaicin/heat ongoing pain (CHOP) model induces long-lasting experimental pain of which the perceived intensity can be individually adjusted. ⋯ Here we demonstrate a novel pain model that can be applied for up to an hour without tissue damage. The CHOP model allows for investigation of primary and secondary hyperalgesia as well as top-down influences on sensitization, thereby providing an experimental model that can be used to assess clinically-oriented questions.
-
Recent studies have implicated that matrix metalloproteinase (MMP)-9 and MMP-2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP-9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases (MMPs). ⋯ Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision-induced microglia TLR4/MMP-9/2/IL-1β signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP-9/2 may provide a new strategy for ameliorating postoperative pain.
-
Pain sensitization after partial infraorbital nerve transection (p-IONX) in mice not only presents in orofacial region, but also spreads to distant body parts. The roles of toll-like receptor 4 (TLR4) in orofacial pain and the spreading process are still unclear. Here, we found that mice with deficient TLR4 because of Tr4 gene point mutation (C3H/HeJ) or spontaneous deletion (C57BL/10ScNJ) developed tactile allodynia and thermal hyperalgesia in the vibrissal pad in a parallel way to their respective wild types (C3HeB/FeJ or C57BL/6J) after p-IONX. ⋯ The hypersensitivity, which did not spread to the vibrissal pad, was accompanied with upregulation of MyD88 in the lumbar cord rather than in the medulla. These results suggest that TLR4 participates in the spread of allodynia component of orofacial pain to distant body sites, but not trigeminal neuropathic pain or the spread of its hyperalgesia component. This study suggests that TLR4 may serve as a potential target for the management of widespread allodynia associated with orofacial pain.
-
Connexin43 (Cx43), involved in intercellular signaling, is expressed in spinal dorsal horn astrocytes and crucial in the maintenance of neuropathic pain. Downregulation of spinal astrocytic Cx43 in mice enhances glutamatergic neurotransmission by decreasing glutamate transporter GLT-1 expression, resulting in cutaneous hypersensitivity. Decreased expression of astrocytic Cx43 could lead to altered expression of other nociceptive molecules. ⋯ Suppression of glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, prevented upregulation of IL-6 and COX-2 expression induced by Cx43 downregulation in both cultured astrocytes and in mouse spinal dorsal horn. Inhibition of spinal GSK-3β also ameliorated Cx43 siRNA-induced mechanical hypersensitivity. The current findings indicate that downregulation of spinal astrocytic Cx43 leads to changes in spinal expression of pronociceptive molecules underlying the maintenance of pain following nerve injury.
-
Neuroscience bulletin · Feb 2018
Involvement of NF-κB and the CX3CR1 Signaling Network in Mechanical Allodynia Induced by Tetanic Sciatic Stimulation.
Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. ⋯ In addition, blockade of NF-κB down-regulated the expression of CX3CL1-CX3CR1 signaling, and conversely the CX3CR1-neutralizing antibody also down-regulated pNF-κB. These findings suggest an involvement of NF-κB and the CX3CR1 signaling network in the development and maintenance of TSS-induced mechanical allodynia. Our work suggests the potential clinical application of NF-κB inhibitors or CX3CR1-neutralizing antibodies in treating pathological pain.