Increased pain in response to mechanical or thermal stimulation in a rat model of incision-induced pain with nicotine dependence and withdrawal

Zhang, Zongwang; Liu, Xianwen; Lu, Sufen; Yu, Ailan; Fu, Zhijian

doi:10.3892/etm.2013.963

Cited by 15 publications

(14 citation statements)

References 27 publications

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“…SNI is known to cause denervation of skin and muscle where CGRP␣ staining is nearly gone within the first 2 weeks (Duraku et al, 2012;Nascimento et al, 2015). The lack of effect at early time points may be due to severely reduced CAN innervation where the mechanical hypersensitivity is likely mediated by CGRPnegative fibers that are sensitized by factors released from neighboring injured fibers or support cells (Berta et al, 2014(Berta et al, , 2017Weaver et al, 2017). The most parsimonious explanation for the inhibition that begins at 1 week is that spared collateral CANs reinnervate the hindpaw (Duraku et al, 2012;Nascimento et al, 2015) and continue to maintain transmission of mechanical neuropathic pain chronically.…”

Section: Discussionmentioning

confidence: 99%

“…Then, DRG neurons were mechanically dissociated and plated onto laminin-coated glass coverslips. DRG neurons were incubated overnight in DMEM supplemented with 10% heat-inactivated horse serum, 2 mM L-glutamine, 1% glucose, 100 units/ml penicillin, and 100 g/ml streptomycin (Zappia et al, 2016). No exogenous growth factors were added to the medium.…”

Section: Methodsmentioning

confidence: 99%

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Optogenetic Inhibition of CGRPα Sensory Neurons Reveals Their Distinct Roles in Neuropathic and Incisional Pain

et al. 2018

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Cutaneous somatosensory neurons convey innocuous and noxious mechanical, thermal, and chemical stimuli from peripheral tissues to the CNS. Among these are nociceptive neurons that express calcitonin gene-related peptide-α (CGRPα). The role of peripheral CGRPα neurons (CANs) in acute and injury-induced pain has been studied using diphtheria toxin ablation, but their functional roles remain controversial. Because ablation permanently deletes a neuronal population, compensatory changes may ensue that mask the physiological or pathophysiological roles of CANs, particularly for injuries that occur after ablation. Therefore, we sought to define the role of intact CANs under baseline and injury conditions by using noninvasive transient optogenetic inhibition. We assessed pain behavior longitudinally from acute to chronic time points. We generated adult male and female mice that selectively express the outward rectifying proton pump archaerhodopsin-3 (Arch) in CANs, and inhibited their peripheral cutaneous terminals in models of neuropathic (spared nerve injury) and inflammatory (skin-muscle incision) pain using transdermal light activation of Arch. After nerve injury, brief activation of Arch reversed the chronic mechanical, cold, and heat hypersensitivity, alleviated the spontaneous pain, and reversed the sensitized mechanical currents in primary afferent somata. In contrast, Arch inhibition of CANs did not alter incision-induced hypersensitivity. Instead, incision-induced mechanical and heat hypersensitivity was alleviated by peripheral blockade of CGRPα peptide-receptor signaling. These results reveal that CANs have distinct roles in the time course of pain during neuropathic and incisional injuries and suggest that targeting peripheral CANs or CGRPα peptide-receptor signaling could selectively treat neuropathic or postoperative pain, respectively. The contribution of sensory afferent CGRPα neurons (CANs) to neuropathic and inflammatory pain is controversial. Here, we left CANs intact during neuropathic and perioperative incision injury by using transient transdermal optogenetic inhibition of CANs. We found that peripheral CANs are required for neuropathic mechanical, cold, and heat hypersensitivity, spontaneous pain, and sensitization of mechanical currents in afferent somata. However, they are dispensable for incisional pain transmission. In contrast, peripheral pharmacological inhibition of CGRPα peptide-receptor signaling alleviated the incisional mechanical and heat hypersensitivity, but had no effect on neuropathic pain. These results show that CANs have distinct roles in neuropathic and incisional pain and suggest that their targeting via novel peripheral treatments may selectively alleviate neuropathic versus incisional pain.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Optogenetic Inhibition of CGRPα Sensory Neurons Reveals Their Distinct Roles in Neuropathic and Incisional Pain

et al. 2018

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“…The latency to hind paw withdrawal from a thermal stimulus was determined by exposing the plantar surface of the hind paw to radiant heat using a Thermal Paw Stimulation System (BME-410C, Tianjin) [21][22][23][24]. Rats were placed in a transparent, square, bottomless acrylic box (22 × 12 × 22 cm) on a glass plate with a light located underneath.…”

Section: Measurement Of the Thermal Withdrawal Latencymentioning

confidence: 99%

“…The pressure value was automatically recorded. Measurements were performed 2-3 times for each rat (interval ≥ 5 min), and the mechanical withdrawal threshold was calculated as the mean of these measurements [21][22][23][24].…”

Section: Mechanical Withdrawal Thresholdmentioning

confidence: 99%

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

Xie

Zhou

et al. 2017

Purinergic Signalling

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The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2′,3′-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIVgp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5′-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADPinduced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of proinflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

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“…Em um modelo de dor incisional em ratos viciados em nicotina e privados da droga, os estímulos térmicos e mecânicos aumentaram a sensibilidade à dor. 5 Estudos enfatizaram que o tabagismo é um dos preditivos de dor intensa no período pós-operatório. 18 Em outro estudo, no qual 520 extrações dentárias foram feitas, o tabagismo foi relatado entre os fatores relacionados ao aumento dos níveis de dor após a extração do dente.…”

Section: Discussionunclassified

Efeitos do tabagismo sobre a dor durante o cateterismo venoso: um estudo prospectivo e randomizado

Hancı

Kiraz

Ömür

et al. 2015

Brazilian Journal of Anesthesiology

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Increased pain in response to mechanical or thermal stimulation in a rat model of incision-induced pain with nicotine dependence and withdrawal

Cited by 15 publications

References 27 publications

Optogenetic Inhibition of CGRPα Sensory Neurons Reveals Their Distinct Roles in Neuropathic and Incisional Pain

Optogenetic Inhibition of CGRPα Sensory Neurons Reveals Their Distinct Roles in Neuropathic and Incisional Pain

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

Efeitos do tabagismo sobre a dor durante o cateterismo venoso: um estudo prospectivo e randomizado

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