CC-chemokine MIP-1α in the spinal cord contributes to nerve injury-induced neuropathic pain

Kiguchi, Norikazu; Kobayashi, Yuka; Maeda, Takehiko; Saika, Fumihiro; Kishioka, Shiroh

doi:10.1016/j.neulet.2010.07.085

Cited by 52 publications

(49 citation statements)

References 27 publications

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“…The enhanced presence of CCL3 can also explain the immediate analgesic effects, independent from an anti-inflammatory action, evoked by the administration of the CCR1 antagonist J113863 in carrageenan-and CFA-inflamed mice. These results add new insights to the previously reported information related to the involvement of CCR1 in neuropathic [7,11,12,35] or neoplastic [10] pain. The possibility of inhibiting inflammatory pain following the acute administration of a CCR1 antagonist seems particularly interesting considering that CCR1 antagonists are already being tested in clinical trials, and that a CCR1 antagonist has been shown to improve rheumatoid arthritis without inducing remarkable adverse reactions [21].…”

Section: Discussionsupporting

confidence: 78%

“…The stimulation of CCR1 expressed in nociceptors causes Ca 2+ influx and enhances capsaicin responsiveness [6], and the local administration of CCR1 agonists elicits nociceptive behaviours in mice [9,10]. CCR1 is up-regulated in sensory neurons [11] and the spinal cord [7,12] after nerve injury and increased CCR1 mRNA has also been measured in rats 24 hr after receiving carrageenan [13], supporting its involvement in nociceptive processing. Functionally, it has been reported that some types of neuropathic pain can be alleviated by blocking CCR1 expression with siRNA [11], and that the administration of a CCR1 antagonist can prevent some types of murine bone cancer pain [10] and partially reduce writhing responses in mice receiving intraperitoneal acetic acid or mechanical hyperalgesia in inflamed mice [14].…”

mentioning

confidence: 85%

“…Among the different chemokines able to activate CCR1 [15], CCL3 (MIP-1a, macrophage inflammatory protein-1a) and CCL5 (RANTES, reduced upon activation normal T-cell expressed and secreted) are particularly related to nociception. CCL3 mRNA is up-regulated in the spinal cord of inflamed rats [16] and the spinal expression of CCL3 increases in mice with prostatitis [17] or nerve injury [11] being its neutralization with a specific antibody able to evoke analgesic effects [12]. CCL5 has been also previously related to hypernociceptive reactions associated with neuropathic injury [18] and tumour development [10,19,20].…”

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confidence: 99%

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Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Llorián-Salvador

González-Rodríguez

Lastra

et al. 2016

Basic Clin Pharma Tox

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Chemokines are chemotactic cytokines whose involvement in nociceptive processing is being increasingly recognized. Based on the previous description of the involvement of CC chemokine receptor type 1 (CCR1) in pathological pain, we have assessed the participation of CCR1 and its endogenous ligands CCL3 and CCL5 in hyperalgesia and allodynia in mice after acute inflammation with carrageenan and chronic inflammation with complete Freund's adjuvant (CFA). The subcutaneous administration of the CCR1 antagonist J113863 (3-30 mg/kg; 30 min. before) dose dependently inhibited carrageenan-and CFA-evoked thermal hyperalgesia and mechanical allodynia produced by CFA, but not by carrageenan. The maximal dose of J113863 did not modify the increase in paw thickness induced by carrageenan or CFA. An almost ten times augmentation of CCL3 levels was detected by ELISA assays in both carrageenan and CFA paws, but not in spinal cords of inflamed mice, whereas CCL5 concentrations remained unaltered. Accordingly, a marked increase of CCL3 mRNA expression was observed in inflamed paws, with CCL3 protein detected in neutrophils and macrophages by immunohistochemical experiments. The intraplantar administration of an anti-CCL3 antibody (0.3-3 lg) blocked thermal hyperalgesia in carrageenan-and CFA-inflamed mice as well as CFA-evoked mechanical allodynia. Our data suggest that the increased concentrations of CCL3 present in inflamed tissues can be involved in acute and chronic inflammatory hyperalgesia as well as in chronic mechanical allodynia, and that these hypernociceptive symptoms can be counteracted by its neutralization with an antibody or by the blockade of CCR1 receptors.Chemokines are chemotactic cytokines involved in inflammatory processes, mainly by favouring immune cell recruitment. Several chemokines activate nociceptive pathways at both peripheral and central level, and this explains their participation in different types of pathological pain [1][2][3][4]. CC chemokine receptor type 1 (CCR1) is expressed in neurons of dorsal root ganglia (DRG) [5,6] as well as in central structures related to pain [7,8]. The stimulation of CCR1 expressed in nociceptors causes Ca 2+ influx and enhances capsaicin responsiveness [6], and the local administration of CCR1 agonists elicits nociceptive behaviours in mice [9,10]. CCR1 is up-regulated in sensory neurons [11] and the spinal cord [7,12] after nerve injury and increased CCR1 mRNA has also been measured in rats 24 hr after receiving carrageenan [13], supporting its involvement in nociceptive processing. Functionally, it has been reported that some types of neuropathic pain can be alleviated by blocking CCR1 expression with siRNA [11], and that the administration of a CCR1 antagonist can prevent some types of murine bone cancer pain [10] and partially reduce writhing responses in mice receiving intraperitoneal acetic acid or mechanical hyperalgesia in inflamed mice [14]. Among the different chemokines able to activate CCR1 [15], CCL3 (MIP-1a, macrophage inflammatory protein-1...

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Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 85%

mentioning

confidence: 99%

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Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Llorián-Salvador

González-Rodríguez

Lastra

et al. 2016

Basic Clin Pharma Tox

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“…These mediators are required to activate inflammatory cells including macrophages through the common chemokine receptor (CC-chemokine receptor 5; CCR5). Recently, CCL3/macrophage inflammatory protein-1a (MIP-1a) was found to be up-regulated in the peripheral and central nervous systems after peripheral nerve injury and elicited long-lasting neuropathic pain (Kiguchi et al, 2010a(Kiguchi et al, , 2010b. CCL5 also participates in pain perception (Oh et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

CC‐chemokine ligand 4/macrophage inflammatory protein‐1β participates in the induction of neuropathic pain after peripheral nerve injury

Saika

Kiguchi

Kobayashi

et al. 2012

European Journal of Pain

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Background: Neuropathic pain is caused by neural damage or dysfunction and neuropathic pain-related symptoms are resistant to conventional analgesics. Neuroinflammation due to the cytokine-chemokine network may play a pivotal role in neuropathic pain. We demonstrate that macrophage inflammatory protein-1b (MIP-1b) participates in neuropathic pain. Methods: Mice received partial sciatic nerve ligation (PSL), and tactile allodynia and thermal hyperalgesia were assessed by von Frey test and Hargreaves test, respectively. Agents were administered into the region surrounding the sciatic nerve (SCN). Results: Using reverse transcription polymerase chain reaction, the mRNA expressions of MIP-1b and its receptor (CC-chemokine receptor 5; CCR5) in the injured SCN were up-regulated after PSL. MIP-1b immunoreactivity was localized in macrophages and Schwann cells and increased in the injured SCN on day 1. PSL-induced tactile allodynia on days 4 to 7 was prevented by the administration of MIP-1b neutralizing antibody (anti-MIP-1b; on days 0, 3 and 6). PSL-induced up-regulations of inflammatory cytokine-chemokine mRNAs in the injured SCN were suppressed with anti-MIP-1b treatment on day 7. Administration of CCR5 antagonist, D-alapeptide T-amide (on days 0, 3 and 6) prevented tactile allodynia and thermal hyperalgesia on days 4 to 14. Single administration of recombinant mouse MIP-1b (rmMIP-1b) elicited tactile allodynia. Moreover, rmMIP-1b increased the mRNA expression of inflammatory mediators in the SCN on day 1 after administration. Conclusions: These results suggest that MIP-1b is a novel key mediator, and the peripheral MIP-1b-CCR5 axis contributes to neuropathic pain. Therefore, investigation of this cascade might be a validated approach for the elucidation of neuropathic pain mechanisms.

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“…Subsequently, inflammatory cytokines and chemokines released from the accumulated cells sensitize the primary sensory nerves, 1,2) increasing the release of pain transmitters from the primary sensory nerve endings, resulting in an unusual enhancement of the effect of the pain transmitters on secondary sensory nerves. 3,4) The effect of pain transmitters on secondary sensory nerves is further augmented by the activation of microglia, [5][6][7][8][9] a type of glia cell, in the spinal cord. This accelerates the release of inflammatory cytokines and other factors.…”

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confidence: 99%

Mechanism for Increased Expression of UGT2B in the Liver of Mice with Neuropathic Pain

Kaneta

Ochiai

Nagae

et al. 2016

Biological & Pharmaceutical Bulletin

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Approximately 30% of patients with cancer pain experience concurrent neuropathic pain. Since these patients are not sufficiently responsive to morphine, the development of an effective method of pain relief is urgently needed. Decreased function of the μ opioid receptor, which binds to the active metabolite of morphine M-6-G in the brain, has been proposed as a mechanism for morphine resistance. Previously, we pharmacokinetically examined morphine resistance in mice with neuropathic pain, and demonstrated that the brain morphine concentration was decreased, expression level of P-glycoprotein (P-gp) in the small intestine was increased, and expression level and activity of uridine diphosphate glucuronosyltransferase (UGT)2B in the liver were increased. In order to clarify the mechanism of the increased expression of UGT2B, we examined the phase of neuropathic pain during which UGT2B expression in the liver begins to increase, and whether this increased expression is nuclear receptor-mediated. The results of this study revealed that the increased expression of UGT2B in the liver occurred during the maintenance phase of neuropathic pain, suggesting that it may be caused by transcriptional regulation which was not accompanied by increased nuclear import of pregnane X receptor (PXR). Key words morphine; neuropathic pain; nuclear receptorIt has been reported that the onset of neuropathic pain is closely associated with the immune response around the damaged nerve. When a nerve is injured, histamine, inflammatory cytokines, and chemokines are released from mast cells located in the damaged nerve, inducing the activation and accumulation of neutrophils and macrophages to the nerve site. Subsequently, inflammatory cytokines and chemokines released from the accumulated cells sensitize the primary sensory nerves, 1,2) increasing the release of pain transmitters from the primary sensory nerve endings, resulting in an unusual enhancement of the effect of the pain transmitters on secondary sensory nerves. 3,4) The effect of pain transmitters on secondary sensory nerves is further augmented by the activation of microglia, 5-9) a type of glia cell, in the spinal cord. This accelerates the release of inflammatory cytokines and other factors. It has also been reported that expression of the ligand-gated ion channel pregnane 2 recepter (P2X) receptor is increased in activated microglia. 8,[10][11][12] This induces the release of brain-derived neurotrophic factor (BDNF) from microglia, which binds to the tyrosine kinase receptor B (TrkB) receptor on secondary sensory nerves, downregulating the expression of K-Cl cotransporter 2 (KCC2). 13,14) The reduced expression of KCC2 disinhibits GABAergic neurons, which suppress the sensation of pain under normal conditions, resulting in pain enhancement.15) The expression of P2X receptor and brain-derived neurotrophic factor is also increased by interferon regulatory factor 8 (IRF8), a transcription factor belonging to the interferon regulatory factor family. 16)A recent report states that t...

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CC-chemokine MIP-1α in the spinal cord contributes to nerve injury-induced neuropathic pain

Cited by 52 publications

References 27 publications

Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

Involvement of CC Chemokine Receptor 1 and CCL3 in Acute and Chronic Inflammatory Pain in Mice

CC‐chemokine ligand 4/macrophage inflammatory protein‐1β participates in the induction of neuropathic pain after peripheral nerve injury

Mechanism for Increased Expression of UGT2B in the Liver of Mice with Neuropathic Pain

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