Peripheral and spinal circuits involved in mechanical allodynia

Arcourt, Alice; Lechner, Stefan

doi:10.1097/01.j.pain.0000460818.62406.38

Cited by 19 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differences in Cl − gradients between nociceptive and non-nociceptive afferents may contribute to the latter being more sensitive to disinhibition 10, 33, 36, 46–48 . In Hirudo this disinhibition selectively affects non-nociceptive pathways, but may have effects on both non-nociceptive and nociceptive pathways in mammals possibly due to the more complex circuitry (in terms of multiple classes of inhibitory and excitatory interneurons) at the spinal cord level 14, 15 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli

Summers

Hanten

Peterson

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain. However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo. Hirudo were injected with either the 2-arachidonoylglycerol (2-AG) or anandamide and tested for changes in response to nociceptive and non-nociceptive stimuli. Both endocannabinoids enhanced responses to non-nociceptive stimuli and reduced responses to nociceptive stimuli. These pro- and anti-nociceptive effects were blocked by co-injection of a TRPV channel inhibitor, which are thought to function as an endocannabinoid receptor. In experiments to determine the effects of endocannabinoids on animals that had undergone injury-induced sensitization, 2-AG and anandamide diminished sensitization to nociceptive stimuli although the effects of 2-AG were longer lasting. Sensitized responses to non-nociceptive stimuli were unaffected 2-AG or anandamide. These results provide evidence that endocannabinoids can have opposing effects on nociceptive vs. non-nociceptive pathways and suggest that cannabinoid-based therapies may be more appropriate for treating pain disorders in which hyperalgesia and not allodynia is the primary symptom.

show abstract

Section: Discussionmentioning

confidence: 99%

“…An especially difficult issue involves examining the potential role of non-nociceptive afferents that have access to nociceptive microcircuits 14, 15 . This access is regulated by inhibitory neurons that effectively control or “gate” whether non-nociceptive afferents have input to nociceptive microcircuits 16–18 .…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli

Summers

Hanten

Peterson

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…This is difficult to treat using conventional analgesics such as opioid or NSAIDS, and it impacts greatly upon quality of life due to the pervasive nature of mechanical stimuli; for example, small movements of the body, or the weight of clothing can cause severe pain in neuropathic patients 2 . While much recent progress has been made in delineating the spinal circuits that gate mechanical pain 3 – 6 , the identity of the sensory neurons that input this sensation into the spinal cord is less clear 7 .…”

Section: Introductionmentioning

confidence: 99%

Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons

et al. 2018

Self Cite

View full text Add to dashboard Cite

Mechanical allodynia is a major symptom of neuropathic pain whereby innocuous touch evokes severe pain. Here we identify a population of peripheral sensory neurons expressing TrkB that are both necessary and sufficient for producing pain from light touch after nerve injury in mice. Mice in which TrkB-Cre-expressing neurons are ablated are less sensitive to the lightest touch under basal conditions, and fail to develop mechanical allodynia in a model of neuropathic pain. Moreover, selective optogenetic activation of these neurons after nerve injury evokes marked nociceptive behavior. Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain. Thus we identify the peripheral neurons which transmit pain from light touch and uncover a novel pharmacological strategy for its treatment.

show abstract

“…The answer to this question is depicted in our working model shown in Fig. 6 which is largely inspired from a recent short review by Arcourt and Lechner12. In this model, we propose that C-LTMRs connect an inhibitory interneuron, connected to a second inhibitory interneuron, which itself is connected to an excitatory interneuron.…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain

Urien

Gaillard²,

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Primary sensory neurons are heterogeneous by myriad of molecular criteria. However, the functional significance of this remarkable heterogeneity is just emerging. We precedently described the GINIP+ neurons as a new subpopulation of non peptidergic C-fibers encompassing the free nerve ending cutaneous MRGPRD+ neurons and C-LTMRs. Using our recently generated ginip mouse model, we have been able to selectively ablate the GINIP+ neurons and assess their functional role in the somatosensation. We found that ablation of GINIP+ neurons affected neither the molecular contents nor the central projections of the spared neurons. GINIP-DTR mice exhibited impaired sensation to gentle mechanical stimuli applied to their hairy skin and had normal responses to noxious mechanical stimuli applied to their glabrous skin, under acute and injury-induced conditions. Importantly, loss of GINIP+ neurons significantly altered formalin-evoked first pain and drastically suppressed the second pain response. Given that MRGPRD+ neurons have been shown to be dispensable for formalin-evoked pain, our study suggest that C-LTMRs play a critical role in the modulation of formalin-evoked pain.

show abstract

Peripheral and spinal circuits involved in mechanical allodynia

Cited by 19 publications

References 19 publications

Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli

Endocannabinoids Have Opposing Effects On Behavioral Responses To Nociceptive And Non-nociceptive Stimuli

Control of mechanical pain hypersensitivity in mice through ligand-targeted photoablation of TrkB-positive sensory neurons

Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain

Contact Info

Product

Resources

About