Primary afferent-driven presynaptic inhibition of C-fiber inputs to spinal lamina I neurons

Fernandes, Elisabete C; Pechincha, C.; Luz, Liliana L.; Kókai, Éva; Szûcs, Péter; Safronov, Boris V.

doi:10.1016/j.pneurobio.2020.101786

Cited by 17 publications

(46 citation statements)

References 62 publications

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“…38,63 Despite this, PVIN photostimulation evoked excitatory input in laminae I-IIo, suggesting most of these cells receive PVIN input through ventrally directed dendrites. 14,25,48,73 Our data that lamina I PNs also receive direct PVIN input suggest a similar arrangement of dendritic extensions into the PVIN plexus. This is supported by our recent characterisation of mouse lamina I PNs, demonstrating dendritic arbours extend more ventral than previously appreciated.…”

Section: Discussionmentioning

confidence: 64%

Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Gradwell

Boyle

Browne

et al. 2021

Pain

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Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs (iPVINs) play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported, and that both ePVIN and iPVIN populations form synaptic connections amongst (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits, and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.

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Section: Discussionmentioning

confidence: 64%

Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Gradwell

Boyle

Browne

et al. 2021

Pain

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“…of C-fiber inputs may be involved. C-fiber-driven inhibition of C-fibers functioned as a feedforward mechanism, by which the homotypic afferents control sensory information flowing into the spinal cord (Zimmerman et al, 2019;Fernandes et al, 2020). Further investigation should be performed to elucidate whether the descending pain inhibitory system or presynaptic inhibition mediates noxious MS analgesia.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture and Moxibustion-Like Stimulation Relieves Inflammatory Muscle Pain by Activating Local Distinct Layer Somatosensory Afferent Fibers

et al. 2021

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Recent studies have shown that both superficial and deep acupuncture produced clinically relevant and persistent effect on chronic pain, and several subtypes of somatic primary afferents played critical roles in acupuncture and moxibustion analgesia. However, which kind of primary afferents in the superficial and deep tissue of the acupoint is activated by acupuncture or moxibustion to relieve pain persistently remains unclear. The aim of this study is to investigate the roles of distinct peripheral afferents in different layers of the tissue (muscle or skin) in the acupoint for pain relief. Muscular A-fibers activated by deep electroacupuncture (dEA) with lower intensity (approximately 1 mA) persistently alleviated inflammatory muscle pain. Meanwhile, cutaneous C-nociceptors excited by noxious moxibustion-like stimulation (MS) and topical application of capsaicin (CAP) on local acupoint area produced durable analgesic effect. Additionally, spontaneous activity of C-fibers caused by muscular inflammation was also inhibited by dEA and CAP. Furthermore, decreases in pain behavior induced by dEA disappeared after deep A-fibers were demyelinated by cobra venom, whereas CAP failed to relieve pain following cutaneous denervation. Collectively, these results indicate that dEA and MS ameliorate inflammatory muscle pain through distinct primary afferents in different layers of somatic tissue; the former is achieved by activating muscular A-fibers, while the latter is mediated by activating cutaneous C-fibers.

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“…Pinto et al found that the strongest Aδ and C fiber inputs to neurons in lamina Ⅰ were from arborizations coming from the root of the caudal segment, followed by the root projecting to the spinal segment containing that neuron [ 108 ]. Fernandes et al reported that C fiber inhibition is strongest at a given segment when afferents of a caudal segment that project to it are activated via noxious stimulation [ 109 ]. Interestingly, needling along an area with sensory projection spanning within the rostro-caudal extent of 2–3 spinal segments of an injured spinal nerve has proved to relieve mechanical hypersensitivity in animal models of NP [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…ious stimulation [109]. Interestingly, needling along an area with sensory projection spanning within the rostro-caudal extent of 2-3 spinal segments of an injured spinal nerve has proved to relieve mechanical hypersensitivity in animal models of NP [18].…”

Section: Intersegmental Approachmentioning

confidence: 99%

Needling Interventions for Sciatica: Choosing Methods Based on Neuropathic Pain Mechanisms—A Scoping Review

Perreault

Fernández‐de‐las‐Peñas

Cummings³

et al. 2021

JCM

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Sciatica is a condition often accompanied by neuropathic pain (NP). Acupuncture and dry needling are common treatments for pain, and the current literature supports acupuncture as an effective treatment for sciatica. However, it is unknown if the mechanisms of NP are considered in the delivery of needling interventions for sciatica. Our objective was to assess the efficacy and the effectiveness of needling therapies, to identify common needling practices and to investigate if NP mechanisms are considered in the treatment of sciatica. A scoping review of the literature on needling interventions for sciatica and a review of the literature on mechanisms related to NP and needling interventions were performed. Electronic literature searches were conducted on PubMed, MEDLINE, CINAHL and Cochrane Database of Systematic Reviews from inception to August, 2020 to identify relevant papers. Reference lists of included papers were also manually screened and a related-articles search through PubMed was performed on all included articles. Mapping of the results included description of included studies, summary of results, and identification of gaps in the existing literature. Ten articles were included. All studies used acupuncture for the treatment of sciatica, no studies on dry needling were identified. Current evidence supports the efficacy and effectiveness of acupuncture for sciatica, however, no studies considered underlying NP mechanisms in the acupuncture approach for sciatica and the rationale for using acupuncture was inconsistent among trials. This review reveals that neuropathic pain mechanisms are not routinely considered in needling approaches for patients with sciatica. Studies showed acupuncture to be an effective treatment for sciatic pain, however, further research is warranted to explore if needling interventions for sciatica and NP would be more effective if NP mechanisms are considered.

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Primary afferent-driven presynaptic inhibition of C-fiber inputs to spinal lamina I neurons

Cited by 17 publications

References 62 publications

Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Electroacupuncture and Moxibustion-Like Stimulation Relieves Inflammatory Muscle Pain by Activating Local Distinct Layer Somatosensory Afferent Fibers

Needling Interventions for Sciatica: Choosing Methods Based on Neuropathic Pain Mechanisms—A Scoping Review

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