Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

Peirs, Cédric; Williams, Sean-Paul G.; Zhao, Xinyi; Arokiaraj, Cynthia M.; Ferreira, David Wilson; Noh, Myung-chul; Smith, Kelly M.; Halder, Priyabrata; Corrigan, Kelly A.; Gedeon, Jeremy Y.; Lee, Alex S.; Gatto, Graziana; Chi, David; Ross, Sarah E.; Goulding, Martyn; Seal, Rebecca P.

doi:10.1016/j.neuron.2020.10.027

Cited by 137 publications

(141 citation statements)

References 68 publications

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“…Second, post-sensory neurons receiving thermal and proprioceptive information are mostly segregated along the dorso-ventral axis highlighting the functional separation of the dorsal and ventral spinal cord for sensory processing and motor control, respectively. Third, at a finer level of resolution, the anatomical organization of post-sensory circuits in the dorsal horn reflects the recently described functional specialization of superficial spinal interneurons in laminae I-IIo for encoding reflexes mediated by inflammatory and noxious stimuli, and of deeper interneurons in laminae IIi-IV for sensory-motor behaviours driven by mechanical inputs (Gatto et al, 2021; Peirs et al, 2021). Interneurons labeled in TRPV1 HTB experiments, that include afferents detecting noxious thermal stimuli are present at higher density in lamina I and IIo, neatly segregated from the ones traced in PV HTB experiments, representing inputs relaying proprioceptive and cutaneous mechanoreceptive information, that are found in deeper layers starting from lamina IIi.…”

Section: Discussionmentioning

confidence: 69%

“…Recent studies demonstrated the importance of topographic organization of dorsal spinal interneurons for encoding reflexes mediated by inflammatory and noxious stimuli (Gatto et al, 2021; Peirs et al, 2021). Thus, we asked whether the distribution of neurons labelled in PV HTB , TRPV1 HTB , and TRPM8 HTB may reveal the anatomical basis for the functional specificity of spinal somatosensory circuits.…”

Section: Resultsmentioning

confidence: 99%

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Rabies anterograde monosynaptic tracing reveals organization of spinal sensory circuits

Pimpinella

Zampieri

2021

Preprint

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Somatosensory neurons detect vital information about the environment and internal status of the body, such as temperature, touch, itch and proprioception. The circuit mechanisms controlling the coding of somatosensory information and the generation of appropriate behavioral responses are not clear yet. In order to address this issue, it is important to define the precise connectivity patterns between primary sensory afferents dedicated to the detection of different stimuli and recipient neurons in the central nervous system. In this study we used a rabies tracing approach for mapping spinal circuits receiving sensory input from distinct, genetically defined, modalities. We analyzed the anatomical organization of spinal circuits involved in coding of thermal and mechanical stimuli and showed that somatosensory information from distinct modalities is relayed to partially overlapping ensembles of interneurons displaying stereotyped laminar organization, thus highlighting the importance of positional features and population coding for the processing and integration of somatosensory information.

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Section: Discussionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

Rabies anterograde monosynaptic tracing reveals organization of spinal sensory circuits

Pimpinella

Zampieri

2021

Preprint

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“…Therefore, it is possible that the responses to all stimuli may not be shared across species and assumptions about how rats will behave based on mouse studies should be treated with caution. For measuring mechanical allodynia following inflammatory or neuropathic pain, VFHs are probably still a useful mechanical stimulus because of their graded nature of delivering defined forces (Peirs et al, 2021;Wilson et al, 2019). However, when using VFHs during baseline conditions in rats, it is likely that researchers are measuring touch and not pain behavioral responses.…”

Section: Discussionmentioning

confidence: 99%

Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

Foster

et al. 2021

Preprint

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Parental exposure to drugs of abuse such as opioids can have profound and long lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long term paternal exposure to morphine on offspring sensitivity to morphine-derived antinociception during painful experiences. To address this question, we constructed a rat pain scale at millisecond timescales to measure mechanical nociception in a multigenerational morphine exposure paradigm. Surprisingly, while developing the pain scale, we found that von Frey hair filaments (VFHs), the most common stimuli used in pain research, are not painful to rats and morphine did not change the touch-like responses elicited by VFHs. We next deployed this novel pain scale to determine whether chronic morphine exposure in sires impacted pain sensitivity in the next generation. Offspring produced from a cross of morphine treated sires and drug-naive dams, did not show any baseline changes in sensitivity to mechanical nociception. However, morphine-sired male progeny displayed a higher sensitivity to the antinociceptive properties of morphine, as measured by our pain scale. These findings demonstrate that long term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent generation.

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“…Selective ablation of DYN+ neurons (by using an intersectional genetic strategy leading to the neuron-specific expression of the diphtheria toxin receptor) generates spontaneous mechanical allodynia and Aβ fiber-mediated action potential firing in superficial dorsal horn neurons. A more recent study [ 90 ] identified specific subpopulations of excitatory interneurons involved in different forms of mechanical allodynia: By using chemogenetic approaches, allowing the selective inhibition of different classes of neurons, the authors demonstrated that CR+, CCK+, and V-Glut3+ neurons are involved in mechanical allodynia in inflammatory models, while PKCγ+ (together with CCK+ and V-Glut3+) neurons are critical for allodynia induced by nerve injury.…”

Section: Modifications Of Presynaptic Inhibition In Chronic Painmentioning

confidence: 99%

Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits

Comitato

Bardoni

2021

IJMS

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Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regulation of the amount and timing of neurotransmitter release critically affects the integration of postsynaptic responses and the coding of sensory information. The role of GABA (γ-aminobutyric acid) receptors expressed on afferent central terminals is particularly important in sensory processing, both in physiological conditions and in sensitized states induced by chronic pain. During the last decade, techniques of opto- and chemogenetic stimulation and neuronal selective labeling have provided interesting insights on this topic. This review focused on the recent advances about the modulatory effects of presynaptic GABAergic receptors in spinal cord dorsal horn and the neural circuits involved in these mechanisms.

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Mechanical Allodynia Circuitry in the Dorsal Horn Is Defined by the Nature of the Injury

Cited by 137 publications

References 68 publications

Rabies anterograde monosynaptic tracing reveals organization of spinal sensory circuits

Rabies anterograde monosynaptic tracing reveals organization of spinal sensory circuits

Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits

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