VR1, but not P2X3, increases in the spared L4 DRG in rats with L5 spinal nerve ligation

Fukuoka, Tetsuo; Tokunaga, Atsushi; Tachibana, Tetsuya; Dai, Yi; Yamanaka, Hiroki; Noguchi, Koichi

doi:10.1016/s0304-3959(02)00067-2

Cited by 176 publications

(110 citation statements)

References 61 publications

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“…If changes in temperature-activated TRP (transient receptor potential) channels are involved in the development of cold pain, these would occur in adjacent ganglia that maintain a connection between the periphery and the spinal cord. Similar changes in gene expression in uninjured ganglia have been described after L5 spinal nerve injury (Fukuoka et al, 1998(Fukuoka et al, , 2001(Fukuoka et al, , 2002 and chronic constriction of the sciatic nerve (Obata et al, 2003); although these have been primarily attributed to the peripheral intermingling of degenerating and intact axons, degenerating centrally projecting axons may likewise influence their intact neighbors within spinal gray matter. Alternate mechanisms for the development of cold hyperalgesia involve increases in the excitability in the peripheral terminals of cold-sensitive neurons and/or increases in the sensitivity of higher-order neurons to glutamate (Woolf and Salter, 2000).…”

Section: Cold Pain Induced By Cervical Rhizotomymentioning

confidence: 61%

Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy

Ramer

Borisoff²,

Ramer³

2004

J. Neurosci.

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Dorsal rhizotomy results in primary deafferentation of the dorsal horn with concomitant sprouting of spared intraspinal monoaminergic axons. Because descending monoaminergic systems are thought to mitigate nociceptive transmission from the periphery and because dorsal rhizotomy can result in neuropathic pain, we sought to determine whether the rhizotomy-induced sprouting response could be further augmented. Because myelin-derived molecules mask endogenous plasticity of CNS axons and because myelin-inhibitory signaling occurs through the Rho-GTPase pathway, we inhibited Rho-pathway signaling after cervical dorsal rhizotomy in rats. An increase in the density of serotonergic-and tyrosine hydroxylase-positive fibers was seen in the dorsal horn 1 week after septuple rhizotomy, and axon density continued to increase for at least 1 month. One week after septuple rhizotomy, administration of intrathecal Y-27632, an antagonist of Rho-kinase (ROCK), increased the density of both fiber types over vehicle-treated controls. To examine behavioral effects of both cervical rhizotomy and ROCK inhibition, we examined responses to evoked pain: mechanical and thermal allodynia and cold hyperalgesia in the forepaw were examined after single, double, and quadruple rhizotomies of dorsal roots of the brachial plexus. The most notable behavioral outcome was the development of cold hyperalgesia in the affected forepaw after rhizotomies of the C7 and C8 dorsal roots. Application of Y-27632 both attenuated cold hyperalgesia and induced monoaminergic plasticity after C7/8 rhizotomy. Thus, inhibition of Rho-pathway signaling both promoted the sprouting of intact supraspinal monoaminergic fibers and alleviated pain after dorsal rhizotomy.

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Section: Cold Pain Induced By Cervical Rhizotomymentioning

confidence: 61%

Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy

Ramer

Borisoff²,

Ramer³

2004

J. Neurosci.

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“…Neuropathic pain was induced by ligating the L5 spinal nerve as in previous research [12]. With sodium pentobarbital anesthesia (50 mg/kg body weight, i.p.…”

Section: Methodsmentioning

confidence: 99%

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Jiang

et al. 2016

Purinergic Signalling

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Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons.

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“…After SNL, expression of various neuroactive agents, receptors, and channels implicated in nociceptive transmission is increased. These include neuropeptides (Fukuoka et al, 1998), neurotrophins , sodium channels (Porreca et al, 1999), and vanilloid-receptor 1 (Hudson et al, 2001;Fukuoka et al, 2002). Exogenous TNF may stimulate injured DRG by triggering one or more cascades, e.g., stimulating production of neurotrophins (Lindholm et al, 1987;Yoshida and Gage, 1992;Hattori et al, 1996,), which in turn may trigger sensitizing neuropeptides or further enhance DRG neuronal responses to capsaicin (Nicol et al, 1997).…”

Section: Sensitization Of Injured Primary Afferents To Tnfmentioning

confidence: 99%

Increased Sensitivity of Injured and Adjacent Uninjured Rat Primary Sensory Neurons to Exogenous Tumor Necrosis Factor-α after Spinal Nerve Ligation

Schäfers¹,

et al. 2003

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Tumor necrosis factor-␣ (TNF) is upregulated after nerve injury, causes pain on injection, and its blockade reduces pain behavior resulting from nerve injury; thus it is strongly implicated in neuropathic pain. We investigated responses of intact and nerve-injured dorsal root ganglia (DRG) neurons to locally applied TNF using parallel in vivo and in vitro paradigms. In vivo, TNF (0.1-10 pg/ml) or vehicle was injected into L5 DRG in naive rats and in rats that had received L5 and L6 spinal nerve ligation (SNL) immediately before injection. In naive rats, TNF, but not vehicle, elicited long-lasting allodynia. In SNL rats, subthreshold doses of TNF synergized with nerve injury to elicit faster onset of allodynia and spontaneous pain behavior. Tactile allodynia was present in both injured and adjacent uninjured (L4) dermatomes. Preemptive treatment with the TNF antagonist etanercept reduced SNL-induced allodynia by almost 50%. In vitro, the electrophysiological responses of naive, SNL-injured, or adjacent uninjured DRG to TNF (0.1-1000 pg/ml) were assessed by single-fiber recordings of teased dorsal root microfilaments. In vitro perfusion of TNF (100 -1000 pg/ml) to naive DRG evoked shortlasting neuronal discharges. In injured DRG, TNF, at much lower concentrations, elicited earlier onset, markedly higher, and longerlasting discharges. TNF concentrations that were subthreshold in naive DRG also elicited high-frequency discharges when applied to uninjured, adjacent DRG. We conclude that injured and adjacent uninjured DRG neurons are sensitized to TNF after SNL. Sensitization to endogenous TNF may be essential for the development and maintenance of neuropathic pain.

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VR1, but not P2X3, increases in the spared L4 DRG in rats with L5 spinal nerve ligation

Cited by 176 publications

References 61 publications

Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy

Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Increased Sensitivity of Injured and Adjacent Uninjured Rat Primary Sensory Neurons to Exogenous Tumor Necrosis Factor-α after Spinal Nerve Ligation

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