Effects of glucocorticoid receptor antagonists on allodynia and hyperalgesia in mouse model of neuropathic pain

Takasaki, Ichiro; Kurihara, Takashi; Saegusa, Hironao; Zong, Shuqin; Tanabe, Tsutomu

doi:10.1016/j.ejphar.2005.09.045

Cited by 72 publications

(52 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Common to all the neuropathic pain models is a decrease in withdrawal threshold to mechanical or thermal stimulation, which is enhanced after exposure to stress. Studies using GR antagonists, such as mifepristone (MIFE), demonstrated that intrathecal administration could increase both mechanical and thermal withdrawal thresholds in the injured limb (Wang et al, 2004;Takasaki et al, 2005;Gu et al, 2007). Those results were also replicated with intrathecal administration of antisense oligodeoxynucleotides selective for GR (Wang et al, 2004;Dina et al, 2008).…”

Section: Receptors In Stress Pathways That Modulate Nociceptionsupporting

confidence: 62%

Stress-Induced Pain: A Target for the Development of Novel Therapeutics

Johnson

Meerveld

2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Although current therapeutics provide relief from acute pain, drugs used for treatment of chronic pain are typically less efficacious and limited by adverse side effects, including tolerance, addiction, and gastrointestinal upset. Thus, there is a significant need for novel therapies for the treatment of chronic pain. In concert with chronic pain, persistent stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic pain disorders. Stress exacerbation of chronic pain suggests that centrally acting drugs targeting the pain-and stress-responsive brain regions represent a valid target for the development of novel therapeutics. This review provides an overview of how stress modulates spinal and central pain pathways, identifies key neurotransmitters and receptors within these pathways, and highlights their potential as novel targets for therapeutics to treat chronic pain.

show abstract

Section: Receptors In Stress Pathways That Modulate Nociceptionsupporting

confidence: 62%

Stress-Induced Pain: A Target for the Development of Novel Therapeutics

Johnson

Meerveld

2014

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In addition, it was shown that in CCI rats, in line with the creation of mechanical allodynia and thermal hyperalgesia, the thickness of blood corticosterone increased and the expression of the receptor of GR, which is dependent on time, in the posterior spinal cord on the same side of the injured nerve was seen to a great extent. These sector changes were partly resulting from the increase of IL-6 and protein kinase C after creation of CCI (Wang et al, 2004;Takasaki et al, 2005). Also, intraperitoneal injection of the antagonists which are Faryadian et al 965 receptors of glucocorticoids in form of dose-dependent thermal hyperalgesia and mechanical allodynia in the neuropathy model reduced the pain in mouse (Takasaki et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been shown that after CCI, the expression of glucocorticoid receptors (GRs) in the posterior horn of the spinal cord in the same side of the damaged nerve increased with the intervention of IL-6 and protein kinase C, so that the inter-spinal cord injection of anti-serum IL-6 and controlling protein inase C considerably reduced the GR expression and neuropathy pain behavior (Wang et al, 2004). It was also shown that inter-peritoneal and inter-spinal injection (RU486 glucocorticoids receptors agonist) creates antipain impacts, but its core interior injection has no impact on behavioral response towards the pain (Takasaki et al, 2005). These results show that the anti-pain of RU 486 peripheral injection is mainly mediated through spinal cords.…”

Section: Introductionmentioning

confidence: 93%

“…These sector changes were partly resulting from the increase of IL-6 and protein kinase C after creation of CCI (Wang et al, 2004;Takasaki et al, 2005). Also, intraperitoneal injection of the antagonists which are Faryadian et al 965 receptors of glucocorticoids in form of dose-dependent thermal hyperalgesia and mechanical allodynia in the neuropathy model reduced the pain in mouse (Takasaki et al, 2005). The changes in the activity of the voltage-dependent calcium channels can cause fast and transit changes in the thickness of intra-cell calcium provoking cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The influence of verapamil on the inhibitory effects of corticosterone against neuropathic pain behaviors in rats

Faryadian¹,

Khosravi²,

Hoseein³

et al. 2012

Afr. J. Biotechnol.

View full text Add to dashboard Cite

There are many evidences which indicate that calcium channel related voltage plays an important role on the mechanism of neuropathic pain, but no strong evidence has been found yet on the role played by type-L calcium channel. The aim of this study was to evaluate this role in using a properly designed experiment. This cohort study was carried out on seven groups (eight animals each) of male Wistar rats (200 to 300 g). Chronic constriction nerve injury was performed on rats by loosely ligating their common sciatic nerve. The impact of corticosteron at 15 mg/kg on neuropathic pain behaviors was assessed in the presence or absence of verapamil as an L-VSC channel blocker at 5, 10 or 20 mg/kg. Standard procedures were employed to evaluate the behavioral pain responses including the thermal hyperalgesia and the thermal and mechanical allodynia. Our findings indicate that peripheral administration of corticosterone suppressed both hyperalgesia, and thermal and mechanical allodynia; however, verapamil pretreatment attenuated the effects of corticosterone on both thermal hyperalgesia and mechanical allodynia. In addition, the administration of verapamil alone at high dose (20 mg) suppressed both thermal and mechanical allodynia. These findings show that the inhibitory effects of glucocorticoids on neuropathic pain behaviors, at least in part, may be mediated through L-type VSC channels; but our findings suggest a potential role for glucocorticoids receptors agonists in combination with L-type VSC channels antagonists in the clinical management of neuropathic pain.

show abstract

“…cDNA microarray analysis cDNA microarray analysis was carried out in essentially the same way as described previously (20). Two weeks after spinal nerve injury or sham operation of C57BL/6J mice, L5/6 spinal cords were dissected and collected for RNA preparation.…”

Section: Animal Model Of Spinal Nerve Injurymentioning

confidence: 99%

Peripheral-Type Benzodiazepine Receptor Antagonist Is Effective in Relieving Neuropathic Pain in Mice

et al. 2009

Self Cite

View full text Add to dashboard Cite

Abstract. cDNA microarray analysis showed the expression of peripheral-type benzodiazepine receptor (PBR) mRNA is slightly enhanced in the spinal cord of mice with spinal nerve injury (SNL) as compared with sham-operated mice. PBR transports cholesterol to the mitochondria, where cholesterol is converted to pregnenolone. Pregnenolone is then metabolized to progesterone, an activator of progesterone receptor, and further metabolized to produce allopregnanolone and 3α,21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC), positive allosteric modulators and activators of the GABA A receptor. In the present study, we first tested whether the enhanced PBR expression is causally related to neuropathic pain, and we found that the PBR antagonist PK11195 is effective in reducing SNL-induced mechanical allodynia and thermal hyperalgesia. Next we tested whether the PK11195-induced antinociception is attributable to reduced neurosteroid synthesis, which may possibly lead to reduced activation of the progesterone receptor and/or GABA A receptor. We found that allopregnanolone and 3α,5α-THDOC are effective in reducing the anti-hyperalgesic effect of PK11195, suggesting a partial contribution of reduced GABA A -receptor activation to PK11195-induced antinociception.

show abstract

Effects of glucocorticoid receptor antagonists on allodynia and hyperalgesia in mouse model of neuropathic pain

Cited by 72 publications

References 13 publications

Stress-Induced Pain: A Target for the Development of Novel Therapeutics

Stress-Induced Pain: A Target for the Development of Novel Therapeutics

The influence of verapamil on the inhibitory effects of corticosterone against neuropathic pain behaviors in rats

Peripheral-Type Benzodiazepine Receptor Antagonist Is Effective in Relieving Neuropathic Pain in Mice

Contact Info

Product

Resources

About