Deafferentation hypersensitivity in the rat after dorsal rhizotomy: A possible animal model of chronic pain

Lombard, Marie-Christine; Nashold, Blaine S.; Albé-Fessard, D; Salman, Nada; Sakr, Cesar

doi:10.1016/0304-3959(79)90123-4

Cited by 168 publications

(52 citation statements)

References 11 publications

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“…Autotomy after cervical dorsal root injuries in rodents has been described and is suggestive of chronic pain (Lombard et al, 1979;Abad et al, 1989); however, most available data on rhizotomyinduced pain in animals describes mechanical allodynia that develops ipsilateral to single lumbar rhizotomy at L5 (Colburn et al, 1999;Eschenfelder et al, 2000;Li et al, 2000). Interestingly, we found no evidence of mechanical allodynia subsequent to cervical rhizotomy.…”

Section: Cold Pain Induced By Cervical Rhizotomycontrasting

confidence: 59%

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 Rhizotomycontrasting

confidence: 59%

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

Ramer

Borisoff²,

Ramer³

2004

J. Neurosci.

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“…In cats in which retrogasserian trigeminal rhizotomy had been performed 4-6 weeks before the experi ments, hyperactivity was observed in the trigeminal medullary dorsal horn ( fig. 1), in agreement with previous studies [2,5,6]. We found that PAG stimulation often failed to inhibit such hyperactivity following rhizotomy.…”

Section: Resultssupporting

confidence: 82%

Deafferentation Pain and Stimulation of the Thalamic Sensory Relay Nucleus: Clinical and Experimental Study

Takata¹,

Katayama²,

Yamamoto³

et al. 1985

Stereotact Funct Neurosurg

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This report summarizes our clinical experience in which the effects of both thalamic sensory relay nucleus (TSRN) and periaqueductal gray (PAG) stimulation were tested in the same series of patients with various forms of pain. The clinical data indicated that neurogenic pain due to deafferentation at the level of the peripheral nerves or the spinal cord was often controlled by TSRN stimulation but not by PAG stimulation. We also review the results of our experimental investigations in cats which were undertaken in an attempt to clarify the neurophysiologic basis of such differential clinical effects of TSRN and PAG stimulation. It appeared that abnormal hyperactivity within the trigeminal medullary dorsal horn following retrogasserian rhizotomy was far more frequently inhibited by TSRN stimulation than by PAG stimulation.

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“…Given the role played by afferent traffic in dorsal horn activation and sensitization, it is difficult to dismiss the physiological importance of TNF-evoked activity arising from the injured ganglion. An alternative possibility is that lesions, in addition to blocking afferent throughput, initiate time-dependent dorsal horn activity and behaviorally defined neuropathic pain (Lombard et al, 1979;Lombard and Besson, 1989). In either case, whether arising from the injured or uninjured DRG, or both, both sets of ectopic activity clearly relate to TNF-mediated events.…”

Section: Potential Mechanisms For Tnf-evoked Discharges In Drg Neuronsmentioning

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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Deafferentation hypersensitivity in the rat after dorsal rhizotomy: A possible animal model of chronic pain

Cited by 168 publications

References 11 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

Deafferentation Pain and Stimulation of the Thalamic Sensory Relay Nucleus: Clinical and Experimental Study

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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