Is neuropathic pain caused by the activation of nociceptive-specific neurons due to anatomic sprouting in the dorsal horn?

Blomqvist, Anders; Craig, A. D.

doi:10.1002/1096-9861(20001204)428:1<1::aid-cne1>3.0.co;2-0

Cited by 22 publications

(11 citation statements)

References 62 publications

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“…This comparison was stimulated by the observations of Zhang et al demonstrating that SCS suppressed the tonic activity of both WDR and nociceptive‐specific spinothalamic tract cells . However, previous studies have also shown that the application of noxious mechanical and thermal stimuli to peripheral somatic receptive fields activates a spectrum of both HT and WDR neurons that may process specific components of nociceptive inputs including the processing of spinothalamic tract cells . The present study also showed that SCS increased the pinch responses more in WDR than HT neurons.…”

Section: Discussionsupporting

confidence: 70%

Spinal Cord Stimulation With “Conventional Clinical” and Higher Frequencies on Activity and Responses of Spinal Neurons to Noxious Stimuli: An Animal Study

Farber

Linderoth

et al. 2018

Neuromodulation: Technology at the Neural Interface

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Section: Discussionsupporting

confidence: 70%

Spinal Cord Stimulation With “Conventional Clinical” and Higher Frequencies on Activity and Responses of Spinal Neurons to Noxious Stimuli: An Animal Study

Farber

Linderoth

et al. 2018

Neuromodulation: Technology at the Neural Interface

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“…an up‐regulation of the binding site for CTB, resulting in a marked increase in the capacity of DRG neurons to take up and transport CTB, so that in addition to large neurons, almost all small neurons are labelled (Tong et al ., 1999). These findings strongly suggest that CTB‐labelled fibers in lamina II mainly represent C‐fibers, and seriously question the role of anatomic sprouting as a basis for neuropathic pain, as recently discussed (Blomqvist & Craig, 2000). Our previous results did, however, not rule out the possibility that the injured C‐fibers transport CTB to DRG but not further into the dorsal horn.…”

Section: Introductionmentioning

confidence: 76%

Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord

Liu

Wang

Cai

et al. 2002

Eur J of Neuroscience

106

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Peripheral axotomy-induced sprouting of thick myelinated afferents (A-fibers) from laminae III-IV into laminae I-II of the spinal cord is a well-established hypothesis for the structural basis of neuropathic pain. However, we show here that the cholera toxin B subunit (CTB), a neuronal tracer used to demonstrate the sprouting of A-fibers in several earlier studies, also labels unmyelinated afferents (C-fibers) in lamina II and thin myelinated afferents in lamina I, when applied after peripheral nerve transection. The lamina II afferents also contained vasoactive intestinal polypeptide and galanin, two neuropeptides mainly expressed in small dorsal root ganglion (DRG) neurons and C-fibers. In an attempt to label large DRG neurons and A-fibers selectively, CTB was applied four days before axotomy (pre-injury-labelling), and sprouting was monitored after axotomy. We found that only a small number of A-fibers sprouted into inner lamina II, a region normally innervated by C-fibers, but not into outer lamina II or lamina I. Such sprouts made synaptic contact with dendrites in inner lamina II. Neuropeptide Y (NPY) was found in these sprouts in inner lamina II, an area very rich in Y1 receptor-positive processes. These results suggest that axotomy-induced sprouting from deeper to superficial layers is much less pronounced than previously assumed, in fact it is only marginal. This limited reorganization involves large NPY immunoreactive DRG neurons sprouting into the Y1 receptor-rich inner lamina II. Even if quantitatively small, it cannot be excluded that this represents a functional circuitry involved in neuropathic pain.

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“…Finally, the firing rate of the WDR neuron was the primary output of the network because activity of the WDR neuron correlates with the magnitude of pain following capsaicin injection and because prior studies used WDR activity as a proxy for SCS efficacy (Foreman et al 1976;Guan 2012;Linderoth et al 2009). However, our model does not take into account the activity of all types of projection neurons, such as low-threshold or nociceptive-specific neurons that receive sensory input and contribute to sensory coding (Blomqvist and Craig 2000).…”

Section: Discussionmentioning

confidence: 99%

Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition

Zhang

Janik

Grill

2014

Journal of Neurophysiology

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Spinal cord stimulation (SCS) is a clinical therapy for chronic, neuropathic pain, but an incomplete understanding of the mechanisms underlying SCS contributes to the lack of improvement in SCS efficacy over time. To study the mechanisms underlying SCS, we constructed a biophysically based network model of the dorsal horn circuit consisting of interconnected dorsal horn interneurons and a wide-dynamic range (WDR) projection neuron and representations of both local and surround receptive field inhibition. We validated the network model by reproducing cellular and network responses relevant to pain processing including wind-up, A fiber-mediated inhibition, and surround receptive field inhibition. We then simulated the effects of SCS on the activity of the WDR projection neuron and found that the response of the model WDR neuron to SCS depends on the SCS frequency; SCS frequencies of 30-100 Hz maximally inhibited the model WDR neuron, while frequencies under 30 Hz and over 100 Hz excited the model WDR neuron. We also studied the impacts on the effects of SCS of loss of inhibition due to the loss of either GABA or KCC2 function. Reducing the influence of local and surround GABAergic interneurons by weakening their inputs or their connections to the WDR neuron and shifting the anionic reversal potential of the WDR neurons upward each reduced the range of optimal SCS frequencies and changed the frequency at which SCS had a maximal effect. The results of this study provide insights into the mechanisms of SCS and pave the way for improved SCS parameter selection.

show abstract

Is neuropathic pain caused by the activation of nociceptive-specific neurons due to anatomic sprouting in the dorsal horn?

Cited by 22 publications

References 62 publications

Spinal Cord Stimulation With “Conventional Clinical” and Higher Frequencies on Activity and Responses of Spinal Neurons to Noxious Stimuli: An Animal Study

Spinal Cord Stimulation With “Conventional Clinical” and Higher Frequencies on Activity and Responses of Spinal Neurons to Noxious Stimuli: An Animal Study

Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord

Modeling effects of spinal cord stimulation on wide-dynamic range dorsal horn neurons: influence of stimulation frequency and GABAergic inhibition

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