A Single Nitrous Oxide (N2O) Exposure Leads to Persistent Alleviation of Neuropathic Pain in Rats

Bessière, Baptiste; Laboureyras, Emilie; Chateauraynaud, Jeremy; Laulin, Jean‐Paul; Simonnet, Guy

doi:10.1016/j.jpain.2009.05.003

Cited by 31 publications

(24 citation statements)

References 54 publications

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“…Bilateral allodynia induced by unilateral sciatic nerve CCI is demonstrated in this study supporting previous findings [5,15,43,51,55,64,65,82]. Reports demonstrating bilateral biochemical changes in lumbar spinal cord substantiate these behavioral observations.…”

Section: Discussionsupporting

confidence: 92%

Intrathecal cannabilactone CB2R agonist, AM1710, controls pathological pain and restores basal cytokine levels

Wilkerson

Gentry

Dengler

et al. 2012

Pain

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Spinal glial and proinflammatory cytokine actions are strongly implicated in pathological pain. Spinal administration of the anti-inflammatory cytokine, interleukin-10 (IL-10) abolishes pathological pain and suppresses proinflammatory interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α). Drugs that bind the cannabinoid type 2 receptor (CB2R) expressed on spinal glia reduce mechanical hypersensitivity. To better understand the CB2R-related anti-inflammatory profile of key anatomical nociceptive regions, we assessed mechanical hypersensitivity and protein profiles following intrathecal application of the cannabilactone CB2R agonist, AM1710, in two animal models; unilateral sciatic nerve chronic constriction injury(CCI), and spinal application of HIV-1 glycoprotein 120 (gp120), a model of peri-spinal immune activation. In CCI animals, lumbar dorsal spinal cord and corresponding dorsal root ganglia (DRG) were evaluated by immunohistochemistry for expression of IL-10, IL-1β, phosphorylated p38-mitogen-activated-kinase (p-p38MAPK), a pathway associated with proinflammatory cytokine production, glial cell markers, and degradative endocannabinoid enzymes including monoacyl glycerol lipase (MAGL). AM1710 reversed bilateral mechanical hypersensitivity. CCI revealed decreased IL-10 expression in dorsal spinal cord and DRG while AM1710 resulted in increased IL-10, comparable to controls. Adjacent DRG and spinal sections revealed increased IL-1β, p-p38MAPK, glial markers and/or MAGL expression, while AM1710 suppressed all but spinal p-p38MAPK and microglial activation. In spinal gp120 animals, AM1710 prevented bilateral mechanical hypersensitivity. For comparison to immunohistochemistry, IL-1β and TNF-α protein quantification from lumbar spinal and DRG homogenates was determined, and revealed increased DRG IL-1β protein levels from gp120, that was robustly prevented by AM1710 pretreatment. Cannabilactone CB2R agonists are emerging as anti-inflammatory agents with pain therapeutic implications.

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Section: Discussionsupporting

confidence: 92%

Intrathecal cannabilactone CB2R agonist, AM1710, controls pathological pain and restores basal cytokine levels

Wilkerson

Gentry

Dengler

et al. 2012

Pain

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show abstract

“…The pattern of bilateral allodynia reported in the current study supports a number of prior reports demonstrating a similar behavioral pattern from CCI (Paulson et al 2000, 2002; Spataro et al 2004; Milligan et al 2005a,b; Xu et al 2007; Bessiere et al 2009; Dubovy et al 2010). Bilateral biochemical changes in the spinal cord and the DRG have been examined that may, in part, characterize underlying contralateral allodynia from CCI.…”

Section: Discussionsupporting

confidence: 91%

Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti‐inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia

et al. 2012

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During pathological pain, the actions of the endocannabinoid system, including the cannabinoid 2 receptor (CB2R), leads to effective anti-allodynia and modifies a variety of spinal microglial and astrocyte responses. Here, following spinal administration of the CB2R compound, AM1241, we examined immunoreactive alterations in markers for activated p38 mitogen-activated protein kinase, interleukin-1β (IL-1β), the anti-inflammatory cytokine, interleukin-10 (IL-10) as well as degradative endocannabinoid enzymes, and markers for altered glial responses in neuropathic rats. In these studies, the dorsal horn of the spinal cord and dorsal root ganglia were examined. AM1241 produced profound anti-allodynia with corresponding immunoreactive levels of p38 mitogen-activated kinase, IL-1β, IL-10, the endocannabinoid enzyme monoacylglycerol lipase, and astrocyte activation markers that were similar to nonneuropathic controls. In contrast, spinal AM1241 did not suppress the increased microglial responses observed in neuropathic rats. The differences in fluorescent markers were determined within discrete anatomical regions by applying spectral analysis methods, which virtually eliminated nonspecific signal during the quantification of specific immunofluorescent intensity. These data reveal expression profiles that support the actions of intrathecal AM1241 control pathological pain through anti-inflammatory mechanisms by modulating critical glial factors, and additionally decrease expression levels of endocannabinoid degradative enzymes.

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“…These effects of N 2 O exposure were long-lasting and persisted for at least 4 days following the exposure. A single N 2 O exposure for 75 minutes in rats abolished pain hypersensitivity for at least 1 month (Bessi ere et al, 2010a). A similar observation was reported for Xe-exposure resulted in a delayed preventive effect on pain hypersensitivity, an effect that lasted up to 4 days (Bessi ere et al, 2010b).…”

Section: Discussionsupporting

confidence: 62%

The Effects of Xenon and Nitrous Oxide Gases on Alcohol Relapse

Vengeliene

Bessière

Pype

et al. 2013

Alcohol Clin Exp Res

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A Single Nitrous Oxide (N2O) Exposure Leads to Persistent Alleviation of Neuropathic Pain in Rats

Cited by 31 publications

References 54 publications

Intrathecal cannabilactone CB2R agonist, AM1710, controls pathological pain and restores basal cytokine levels

Intrathecal cannabilactone CB2R agonist, AM1710, controls pathological pain and restores basal cytokine levels

Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti‐inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia

The Effects of Xenon and Nitrous Oxide Gases on Alcohol Relapse

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