Key role of the dorsal root ganglion in neuropathic tactile hypersensibility

Sukhotinsky, Inna; Ben-Dor, Efrat; Raber, Pnina; Devor, Marshall

doi:10.1016/s1090-3801(03)00086-7

Cited by 135 publications

(87 citation statements)

References 62 publications

(87 reference statements)

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“…The present study demonstrated that in the injured L5 DRG, most of the p-ERK-IR neurons and a subpopulation of p-p38-IR neurons were large in size and that the ERK and p38 inhibitors reversed the L5 SNL-induced mechanical allodynia. Furthermore, L5 dorsal rhizotomy prevented the development of mechanical allodynia, as reported previously (Yoon et al, 1996;Sukhotinsky et al, 2004). These observations support the possibility that large-diameter A-fibers mediate mechanical allodynia, whereas nociceptive C-fibers mediate thermal hyperalgesia Pan et al, 2003).…”

Section: Mapk Activation In the Injured L5 Drg Neurons And Mechanicalsupporting

confidence: 88%

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

Obata¹,

Yamanaka²,

Kobayashi³

et al. 2004

J. Neurosci.

290

208

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To investigate whether activation of mitogen-activated protein kinase (MAPK) in damaged and/or undamaged primary afferents participates in neuropathic pain after partial nerve injury, we examined the phosphorylation of extracellular signal-regulated protein kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK) in the L4 and L5 dorsal root ganglion (DRG) in the L5 spinal nerve ligation (SNL) model. We first confirmed, using activating transcription factor 3 and neuropeptide Y immunoreactivity, that virtually all L4 DRG neurons are spared from axotomy in this model. In the injured L5 DRG, the L5 SNL induced the activation of ERK, p38, and JNK in different populations of DRG neurons. In contrast, in the uninjured L4 DRG, the L5 SNL induced only p38 activation in tyrosine kinase A-expressing small-to medium-diameter neurons. Intrathecal ERK, p38, and JNK inhibitor infusions reversed SNL-induced mechanical allodynia, whereas only p38 inhibitor application attenuated SNL-induced thermal hyperalgesia. Furthermore, the L5 dorsal rhizotomy did not prevent SNL-induced thermal hyperalgesia. We therefore hypothesized that p38 activation in the uninjured L4 DRG might be involved in the development of heat hypersensitivity in the L5 SNL model. In fact, the treatment of the p38 inhibitor and also anti-nerve growth factor reduced SNL-induced upregulation of brain-derived neurotrophic factor and transient receptor potential vanilloid type 1 expression in the L4 DRG. Together, our results demonstrate that the L5 SNL induces differential activation of MAPK in injured and uninjured DRG neurons and, furthermore, that MAPK activation in the primary afferents may participate in generating pain hypersensitivity after partial nerve injury.

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Section: Mapk Activation In the Injured L5 Drg Neurons And Mechanicalsupporting

confidence: 88%

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

Obata¹,

Yamanaka²,

Kobayashi³

et al. 2004

J. Neurosci.

290

208

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“…The ectopic firing then leads to initiation and maintenance of central sensitization (Sukhotinsky et al 2004;Devor 2006), most likely due to neurochemical changes taking place in the spinal cord (e.g., Ji and Woolf 2001). In line with this interpretation, when the ectopic peripheral input was suppressed, central sensitization decreased and MA was eliminated (Devor 2006).…”

Section: Introductionmentioning

confidence: 78%

“…As outlined in the Introduction, mechanical allodynia emphasizes its central sensitization, in particular in the dorsal root ganglion or in the dorsal horn (e.g., Woolf 1983;Hendry et al 1999;Mannion et al 1999;Sindrup et al 1999;Ji and Woolf 2001;Ji et al 2003;Sukhotinsky et al 2004;Devor 2006). The statement ''The static mechanical allodynia is a paradoxical painful hypoaesthesia'' does not contest the most likely central component of post-injury pain hypersensitivity (Woolf 1983).…”

Section: Discussionmentioning

confidence: 99%

“…The statement ''The static mechanical allodynia is a paradoxical painful hypoaesthesia'' does not contest the most likely central component of post-injury pain hypersensitivity (Woolf 1983). Few authors remind us that the aetiology of SMA is a damaged nerve (e.g., Woolf and Mannion 1999;Woolf and Salter 2000;Sukhotinsky et al 2004). Bennett (1994) presumed that ''Although [.…”

Section: Discussionmentioning

confidence: 99%

“…A possible reason for the controversies about the mechanisms underlying MA is that MA is fundamentally paradoxical. Partial denervation of the skin is expected to blunt sensation, not to amplify it in a noxious way (Sukhotinsky et al 2004;Devor 2006). The term ''burning numbness'' has been used to describe this paradox (Campa and Payne 1993).…”

Section: Introductionmentioning

confidence: 99%

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Static mechanical allodynia (SMA) is a paradoxical painful hypo-aesthesia: Observations derived from neuropathic pain patients treated with somatosensory rehabilitation

Spicher

Mathis

Degrange

et al. 2008

Somatosensory & Motor Research

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The present study aimed at investigating the time span it takes to remove a static mechanical allodynia (SMA) in humans suffering from chronic peripheral neuropathic pain. Forty-three subjects were included in the study and, during somatosensory rehabilitation, their SMA territory was precisely mapped. They then underwent distant vibrotactile counter stimulation (DVCS) treatment. It was observed that, with DVCS, SMA disappeared in all cases, and was transformed into an underlying hypoaesthesia. It was found that the ''tenderness to touch'' symptom (which is SMA) was located in the same territory as the underlying hypoaesthesia, which was located on a part of the cutaneous territory of a partially damaged nerve. These results demonstrate that treating patients suffering from neuropathic pain with DVCS revealed a skin territory of denervation that was previously masked by SMA. Thus, SMA can be considered as a paradoxical painful hypoaesthesia. Furthermore, mapping SMA is a valuable source of information for our understanding of abnormal sensory processing in neuropathic pain patients. We conclude that the mapping of the zone of hypersensitivity on the skin in humans suffering from chronic peripheral neuropathic pain improves diagnosis. The mapping of the zone of hypersensitivity is a tool to presume which branch of the peripheral nerve is damaged. The location of the axonal lesions is at the periphery, while the mechanism of pain sensitization is probably central and referred peripherally to the skin by a painful hypoaesthesia.

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Differential hypertrophy and atrophy among all types of cutaneous innervation in the glabrous skin of the monkey hand during aging and naturally occurring type 2 diabetes

Paré

Albrecht

Noto

et al. 2007

J of Comparative Neurology

106

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Diabetic neuropathy (DN) is a common severe complication of type 2 diabetes. The symptoms of chronic pain, tingling, and numbness are generally attributed to small fiber dysfunction. However, little is known about the pathology among innervation to distal extremities, where symptoms start earliest and are most severe, and where the innervation density is the highest and includes a wide variety of large fiber sensory endings. Our study assessed the immunochemistry, morphology, and density of the nonvascular innervation in glabrous skin from the hands of aged nondiabetic rhesus monkeys and from age-matched monkeys that had different durations of spontaneously occurring type 2 diabetes. Age-related reductions occurred among all types of innervation, with epidermal C-fiber endings preferentially diminishing earlier than presumptive Adelta-fiber endings. In diabetic monkeys epidermal innervation density diminished faster, became more unevenly distributed, and lost immunodetectable expression of calcitonin gene-related peptide and capsaicin receptors, TrpV1. Pacinian corpuscles also deteriorated. However, during the first few years of hyperglycemia, a surprising hypertrophy occurred among terminal arbors of remaining epidermal endings. Hypertrophy also occurred among Meissner corpuscles and Merkel endings supplied by Abeta fibers. After longer-term hyperglycemia, Meissner corpuscle hypertrophy declined but the number of corpuscles remained higher than in age-matched nondiabetics. However, the diabetic Meissner corpuscles had an abnormal structure and immunochemistry. In contrast, the expanded Merkel innervation was reduced to age-matched nondiabetic levels. These results indicate that transient phases of substantial innervation remodeling occur during the progression of diabetes, with differential increases and decreases occurring among the varieties of innervation.

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Key role of the dorsal root ganglion in neuropathic tactile hypersensibility

Cited by 135 publications

References 62 publications

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

Static mechanical allodynia (SMA) is a paradoxical painful hypo-aesthesia: Observations derived from neuropathic pain patients treated with somatosensory rehabilitation

Differential hypertrophy and atrophy among all types of cutaneous innervation in the glabrous skin of the monkey hand during aging and naturally occurring type 2 diabetes

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