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Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ-afferent neurons after L5 spinal nerve axotomy and are not mediated by HCN channels.
Exp Physiol. 2018 08; 103(8):1145-1156.EP

Abstract

NEW FINDINGS

What is the central question of this study? Is spontaneous activity (SA) in L4 dorsal root ganglion (DRG) neurons induced by L5 spinal nerve axotomy associated with membrane potential oscillations in these neurons, and if so, are these membrane oscillations mediated by HCN channels? What is the main finding and its importance? Unlike injured L5 DRG neurons, which have been shown to be incapable of firing spontaneously without membrane potential oscillations, membrane potential oscillations are not essential for SA generation in conducting 'uninjured' L4 neurons, and they are not mediated by HCN channels. These findings suggest that the underlying cellular mechanisms of SA in injured and 'uninjured' DRG neurons induced by spinal nerve injury are distinct.

ABSTRACT

The underlying cellular and molecular mechanisms of peripheral neuropathic pain are not fully understood. However, preclinical studies using animal models suggest that this debilitating condition is driven partly by aberrant spontaneous activity (SA) in injured and uninjured dorsal root ganglion (DRG) neurons, and that SA in injured DRG neurons is triggered by subthreshold membrane potential oscillations (SMPOs). Here, using in vivo intracellular recording from control L4-DRG neurons, and ipsilateral L4-DRG neurons in female Wistar rats that had previously undergone L5 spinal nerve axotomy (SNA), we examined whether conducting 'uninjured' L4-DRG neurons in SNA rats exhibit SMPOs, and if so, whether such SMPOs are associated with SA in those L4 neurons, and whether they are mediated by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We found that 7 days after SNA: (a) none of the control A- or C-fibre DRG neurons showed SMPOs or SA, but 50%, 43% and 0% of spontaneously active cutaneous L4 Aβ-low threshold mechanoreceptors, Aβ-nociceptors and C-nociceptors exhibited SMPOs, respectively, in SNA rats with established neuropathic pain behaviors; (b) neither SMPOs nor SA in L4 Aβ-neurons was suppressed by blocking HCN channels with ZD7288 (10 mg kg-1 , i.v.); and (c) there is a tendency for female rats to show greater pain hypersensitivity than male rats. These results suggest that SMPOs are linked to SA only in some of the conducting L4 Aβ-neurons, that such oscillations are not a prerequisite for SA generation in those L4 A- or C-fibre neurons, and that HCN channels are not involved in their electrogenesis.

Authors+Show Affiliations

Department of Physiology, College of Medicine, Alfaisal University, PO Box 50927, Riyadh, 11533, Saudi Arabia.Wolfson CARD, Neurorestoration Group, Hodgkin Building, King's College London, Guy's Campus, London, SE1 1UL, UK.Department of Physiology, College of Medicine, King Saud University, PO Box 7805, Riyadh, 11472, Saudi Arabia.Department of Neurobiology and State Key Laboratory of Proteomics, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29860719

Citation

Djouhri, L, et al. "Membrane Potential Oscillations Are Not Essential for Spontaneous Firing Generation in L4 Aβ-afferent Neurons After L5 Spinal Nerve Axotomy and Are Not Mediated By HCN Channels." Experimental Physiology, vol. 103, no. 8, 2018, pp. 1145-1156.
Djouhri L, Smith T, Alotaibi M, et al. Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ-afferent neurons after L5 spinal nerve axotomy and are not mediated by HCN channels. Exp Physiol. 2018;103(8):1145-1156.
Djouhri, L., Smith, T., Alotaibi, M., & Weng, X. (2018). Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ-afferent neurons after L5 spinal nerve axotomy and are not mediated by HCN channels. Experimental Physiology, 103(8), 1145-1156. https://doi.org/10.1113/EP087013
Djouhri L, et al. Membrane Potential Oscillations Are Not Essential for Spontaneous Firing Generation in L4 Aβ-afferent Neurons After L5 Spinal Nerve Axotomy and Are Not Mediated By HCN Channels. Exp Physiol. 2018;103(8):1145-1156. PubMed PMID: 29860719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ-afferent neurons after L5 spinal nerve axotomy and are not mediated by HCN channels. AU - Djouhri,L, AU - Smith,T, AU - Alotaibi,M, AU - Weng,X, Y1 - 2018/06/26/ PY - 2018/03/13/received PY - 2018/05/23/accepted PY - 2018/6/4/pubmed PY - 2019/4/17/medline PY - 2018/6/4/entrez KW - in vivo electrophysiology KW - ion channels KW - neuropathic pain KW - primary sensory neurons SP - 1145 EP - 1156 JF - Experimental physiology JO - Exp Physiol VL - 103 IS - 8 N2 - NEW FINDINGS: What is the central question of this study? Is spontaneous activity (SA) in L4 dorsal root ganglion (DRG) neurons induced by L5 spinal nerve axotomy associated with membrane potential oscillations in these neurons, and if so, are these membrane oscillations mediated by HCN channels? What is the main finding and its importance? Unlike injured L5 DRG neurons, which have been shown to be incapable of firing spontaneously without membrane potential oscillations, membrane potential oscillations are not essential for SA generation in conducting 'uninjured' L4 neurons, and they are not mediated by HCN channels. These findings suggest that the underlying cellular mechanisms of SA in injured and 'uninjured' DRG neurons induced by spinal nerve injury are distinct. ABSTRACT: The underlying cellular and molecular mechanisms of peripheral neuropathic pain are not fully understood. However, preclinical studies using animal models suggest that this debilitating condition is driven partly by aberrant spontaneous activity (SA) in injured and uninjured dorsal root ganglion (DRG) neurons, and that SA in injured DRG neurons is triggered by subthreshold membrane potential oscillations (SMPOs). Here, using in vivo intracellular recording from control L4-DRG neurons, and ipsilateral L4-DRG neurons in female Wistar rats that had previously undergone L5 spinal nerve axotomy (SNA), we examined whether conducting 'uninjured' L4-DRG neurons in SNA rats exhibit SMPOs, and if so, whether such SMPOs are associated with SA in those L4 neurons, and whether they are mediated by hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We found that 7 days after SNA: (a) none of the control A- or C-fibre DRG neurons showed SMPOs or SA, but 50%, 43% and 0% of spontaneously active cutaneous L4 Aβ-low threshold mechanoreceptors, Aβ-nociceptors and C-nociceptors exhibited SMPOs, respectively, in SNA rats with established neuropathic pain behaviors; (b) neither SMPOs nor SA in L4 Aβ-neurons was suppressed by blocking HCN channels with ZD7288 (10 mg kg-1 , i.v.); and (c) there is a tendency for female rats to show greater pain hypersensitivity than male rats. These results suggest that SMPOs are linked to SA only in some of the conducting L4 Aβ-neurons, that such oscillations are not a prerequisite for SA generation in those L4 A- or C-fibre neurons, and that HCN channels are not involved in their electrogenesis. SN - 1469-445X UR - https://www.unboundmedicine.com/medline/citation/29860719/Membrane_potential_oscillations_are_not_essential_for_spontaneous_firing_generation_in_L4_Aβ_afferent_neurons_after_L5_spinal_nerve_axotomy_and_are_not_mediated_by_HCN_channels_ L2 - https://doi.org/10.1113/EP087013 DB - PRIME DP - Unbound Medicine ER -