Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice

Reiss, David J; Maurin, Hervé; Audouard, Emilie; Martínez-Navarro, Miriam; Xue, Ya‐Ping; Hérault, Yann; Maldonado, Rafaël; Cabañero, David; Gavériaux‐Ruff, Claire

doi:10.3389/fncel.2021.745178

Cited by 10 publications

(11 citation statements)

References 74 publications

(113 reference statements)

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“…Further, inhibition of both mu and delta opioid receptors reduced mechanical sensitivity in compression injured rats, implicating these receptors in injury-induced sensitivity 63 . Astrocyte specific knockouts for delta opioid receptors also showed higher mechanical sensitivity threshold to Von Frey stimulation in both males and females, indicating that astrocyte opioid expression may play a key role in mechanical allodynia 67 .…”

Section: Discussionmentioning

confidence: 98%

“…As sustained release Bup works to reduce analgesia for days 19,75 and alterations in opioid signaling in astrocytes alters mechanical sensitivity 67 , the WNT was performed to investigate potential Bup-SR-Labassociated changes in somatosensory sensitivity 4w following cFPI or sham injury. In agreement with previous studies from both our and other groups 24,28,30,31 , animals sustaining cFPI displayed hypersensitivity and agitation to the stimulation as compared with animals sustaining sham injury at 4w post-injury.…”

Section: Discussionmentioning

confidence: 99%

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Post-injury Buprenorphine Administration Is Associated With Long-Term Region-Specific Glial Alterations in Rats

Ryu¹,

Jeizan²,

Ahmed³

et al. 2022

Preprint

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Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manor 4w following diffuse brain injury.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Post-injury Buprenorphine Administration Is Associated With Long-Term Region-Specific Glial Alterations in Rats

Ryu¹,

Jeizan²,

Ahmed³

et al. 2022

Preprint

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“…The secondary binding assay on delta displayed a similarity between the slopes of the standard, naltrindole, and XA. In a study conducted by Reiss D and colleagues 17 , the involvement of the opioid receptor delta in opioid tolerance was discussed. Receptor internalization is a key feature of the activation of the delta opioid receptor.…”

Section: Discussionmentioning

confidence: 99%

Xylopic acid from Xylopia aethiopica (Annonaceae) inhibits morphine tolerance in rats

Mante¹,

Abakah-Ewusi²,

Mingle³

et al. 2022

Pharm Sci Asia

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Traditionally, Xylopia aethiopica is used to manage pain disorders such as neuralgia, colic pain, rheumatism and headache. Using animal models, this study aimed to investigate the ability of Xylopic Acid (XA), a kaurene diterpene obtained from Xylopia aethiopica, to cause tolerance when administered alone or combined with morphine. Development of withdrawal symptoms on discontinuation was also investigated. Tolerance to morphine was induced in rats through an 8-day regimen of chronic administration of morphine (10 mg/kg; twice daily). Effects of XA alone (100 mg/kg) or XA (10-100 mg/kg) on morphine tolerance and withdrawal syndrome precipitated with naloxone hydrochloride (3 mg/kg) were also assessed. XA's mechanism of action was then explored through drug-receptor binding.Chronic morphine administration in rats resulted in analgesic tolerance and morphine withdrawal syndrome. Chronic XA administration did not result in tolerance to XA's antinociceptive effect. Development of morphine withdrawal syndrome precipitated by naloxone and morphine tolerance was significantly (F(12, 60)=29.88, p<0.0001) inhibited by XA. Xylopic acid inhibited development of diarrhea, jumps and weight loss. Pretreatment with α-2-adrenoceptor antagonist, yohimbine, 5HT3 antagonist, ondansetron and muscarinic antagonist, atropine, significantly (p=0.0042) blocked the inhibitory effect of XA on withdrawal jumps. Pretreatment with naloxone produced similar effects on withdrawal jumps as XA alone. Drug-receptor binding assays revealed a lack of significant interaction of XA on alpha-2 adrenoceptors (A, B, C) but exhibited significant DOR-selective antagonism similar to naltrindole. This study reveals that xylopic acid significantly inhibits morphine antinociceptive tolerance and withdrawal in rats. This is the first report of xylopic acid's antagonism on delta opioidergic receptors and potential as an inhibitor of chronic morphine tolerance.

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“…The cold plate assay (Bioseb, Vitrolles, France) was used to assess the sensitivity of the mice to the cold 5°C temperature as described by Reiss et al (2021) . One day before the test, the animals were habituated to the plate at RT in transparent plastic boxes as described above.…”

Section: Methodsmentioning

confidence: 99%

The Human SCN9AR185H Point Mutation Induces Pain Hypersensitivity and Spontaneous Pain in Mice

Xue

Kremer

Moreno

et al. 2022

Front. Mol. Neurosci.

Self Cite

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The voltage-gated sodium channel Nav1.7 is encoded by SCN9A gene and plays a critical role in pain sensitivity. Several SCN9A gain-of-function (GOF) mutations have been found in patients with small fiber neuropathy (SFN) having chronic pain, including the R185H mutation. However, for most of these variants, their involvement in pain phenotype still needs to be experimentally elucidated. In order to delineate the impact of R185H mutation on pain sensitivity, we have established the Scn9aR185H mutant mouse model using the CRISPR/Cas9 technology. The Scn9aR185H mutant mice show no cellular alteration in the dorsal root ganglia (DRG) containing cell bodies of sensory neurons and no alteration of growth or global health state. Heterozygous and homozygous animals of both sexes were investigated for pain sensitivity. The mutant mice were more sensitive than the wild-type mice in the tail flick and hot plate tests, acetone, and von Frey tests for sensitivity to heat, cold, and touch, respectively, although with sexual dimorphic effects. The newly developed bioinformatic pipeline, Gdaphen is based on general linear model (GLM) and random forest (RF) classifiers as well as a multifactor analysis of mixed data and shows the qualitative and quantitative variables contributing the most to the pain phenotype. Using Gdaphen, tail flick, Hargreaves, hot plate, acetone, cold plate, and von Frey tests, sex and genotype were found to be contributing most to the pain phenotype. Importantly, the mutant animals displayed spontaneous pain as assessed in the conditioned place preference (CPP) assay. Altogether, our results indicate that Scn9aR185H mice show a pain phenotype, suggesting that the SCN9AR185H mutation identified in patients with SFN having chronic pain contributes to their symptoms. Therefore, we provide genetic evidence for the fact that this mutation in Nav1.7 channel plays an important role in nociception and in the pain experienced by patients with SFN who have this mutation. These findings should aid in exploring further pain treatments based on the Nav1.7 channel.

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Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice

Cited by 10 publications

References 74 publications

Post-injury Buprenorphine Administration Is Associated With Long-Term Region-Specific Glial Alterations in Rats

Post-injury Buprenorphine Administration Is Associated With Long-Term Region-Specific Glial Alterations in Rats

Xylopic acid from Xylopia aethiopica (Annonaceae) inhibits morphine tolerance in rats

The Human SCN9AR185H Point Mutation Induces Pain Hypersensitivity and Spontaneous Pain in Mice

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