Expression Profiling of Genes Modulated by Minocycline in a Rat Model of Neuropathic Pain

Rojewska, Ewelina; Korostyński, Michał; Przewłocki, Ryszard; Przewłocka, Barbara; Mika, Joanna

doi:10.1186/1744-8069-10-47

Cited by 37 publications

(47 citation statements)

References 84 publications

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“…It is well known that peripheral nerve sensitisation induces changes in the dorsal horn of the spinal cord . The spinal cord is an important anatomical region for gene expression studies involving animal models of pain hypersensitivities . The gene level changes observed in the spinal cord tissue are consistent with the evidence that chronic pain associated with malignant cancer‐induced bone disease is underpinned by sensitisation and synaptic plasticity in the dorsal horn of the spinal cord, that is responsible for amplification of the nociceptive signals and transmission of impulses to higher centres in the brain .…”

Section: Discussionsupporting

confidence: 61%

Transcriptomic characterisation of the optimised rat model of Walker 256 breast cancer cell‐induced bone pain

Shenoy

Kuo

Leparc

et al. 2019

Clin Exp Pharma Physio

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In patients with breast cancer, metastases of cancer cells to the axial skeleton may cause excruciating pain, particularly in the advanced stages. The current drug treatments available to alleviate this debilitating pain condition often lack efficacy and/or produce undesirable side effects. Preclinical animal models of cancer‐induced bone pain are key to studying the mechanisms that cause this pain and for the success of drug discovery programs. In a previous study conducted in our laboratory, we validated and characterised the rat model of Walker 256 cell‐induced bone pain, which displayed several key resemblances to the human pain condition. However, gene level changes that occur in the pathophysiology of cancer‐induced bone pain in this preclinical model are unknown. Hence, in this study, we performed the transcriptomic characterisation of the Walker 256 cell line cultured in vitro to predict the molecular genetic profile of this cell line. We also performed transcriptomic characterisation of the Walker 256 cell‐induced bone pain model in rats using the lumbar spinal cord and lumbar dorsal root ganglia tissues. Here we show that the Walker 256 cell line resembles the basal‐B molecular subtype of human breast cancer cell lines. We also identify several genes that may underpin the progression of pain hypersensitivities in this condition, however, this needs further confirmatory studies. These transcriptomic insights have the potential to direct future studies aimed at identifying various mechanisms underpinning pain hypersensitivities in this model that may also assist in discovery of novel pain therapeutics for breast cancer‐induced bone pain.

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Section: Discussionsupporting

confidence: 61%

Transcriptomic characterisation of the optimised rat model of Walker 256 breast cancer cell‐induced bone pain

Shenoy

Kuo

Leparc

et al. 2019

Clin Exp Pharma Physio

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“…Indeed, whereas Maves et al 50. placed ligatures sliding along the nerve, with no constriction, the ligatures’ tightness that is achieved following the original constriction procedure of Bennett and Xie29 has been regularly reported to produce strong mechanical hyperalgesia not only with chromic gut but also with silk thread around the nerve (see refs 51, 52, 53, 54). Accordingly, marked supersensitivity to mechanical stimulation of ipsilateral hindpaw was also observed after silk thread ligation of the sciatic nerve in CCI-SN rats used in the present study (Figs 3 and 4).…”

Section: Discussionmentioning

confidence: 99%

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Jeanson

Duchêne

Richard

et al. 2016

Sci Rep

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Antidepressants, prescribed as first line treatment of neuropathic pain, have a limited efficacy and poorly tolerated side effects. Because recent studies pointed out the implication of astroglial connexins (Cx) in both neuropathic pain and antidepressive treatment, we investigated whether their blockade by mefloquine could modulate the action of the tricyclic antidepressant amitriptyline. Using primary cultures, we found that both mefloquine and amitriptyline inhibited Cx43-containing gap junctions, and that the drug combination acted synergically. We then investigated whether mefloquine could enhance amitriptyline efficacy in a preclinical model of neuropathic pain. Sprague-Dawley rats that underwent chronic unilateral constriction injury (CCI) to the sciatic nerve (SN) were treated with either amitriptyline, mefloquine or the combination of both drugs. Whereas acute treatments were ineffective, chronic administration of amitriptyline reduced CCI-SN-induced hyperalgesia-like behavior, and this effect was markedly enhanced by co-administration of mefloquine, which was inactive on its own. No pharmacokinetic interactions between both drugs were observed and CCI-SN-induced neuroinflammatory and glial activation markers remained unaffected by these treatments in dorsal root ganglia and spinal cord. Mechanisms downstream of CCI-SN-induced neuroinflammation and glial activation might therefore be targeted. Connexin inhibition in astroglia could represent a promising approach towards improving neuropathic pain therapy by antidepressants.

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“…RU486 (mifepristone; Toronto Research Chemicals, North York, Canada), the GR antagonist, was dissolved in 10 % ethanol solution and intraperitoneally administrated at a dosage of 15 mg/kg. The dosages of minocycline hydrochloride and RU 486 were chosen referring to previous studies [41,42] and based on our preliminary experiment. Both drugs were prepared in a volume of 1.5 ml.…”

Section: Drug Preparationmentioning

confidence: 99%

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

et al. 2016

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Clinically, preoperative anxiety adversely affected postoperative hyperalgesia. As stress-induced glucocorticoids (GCs) were reported to sensitize the activation of microglia, the present study investigated whether and how GCs and microglia played in the process of preoperative anxiety-induced postoperative hyperalgesia. The study used an animal model that exposed rats to single prolonged stress (SPS) procedure to induce preoperative anxiety-like behaviors 24 h before the plantar incisional surgery. Behavioral testing revealed that preoperative SPS enhanced the mechanical allodynia induced by plantar incision. SPS was also found to induce elevated circulating corticosterone levels, potentiate the activation of spinal microglia, and increase the expression of spinal proinflammatory cytokines. Inhibition of microglia by pretreatment with minocycline attenuated the SPS-enhanced mechanical allodynia, and this was accompanied by decreased activation of spinal microglia and expression of proinflammatory cytokines. Another experiment was conducted by administering RU486, the GC receptor (GR) antagonist, to rats. The results showed that RU486 suppressed SPS-induced and SPS-potentiated proinflammatory activation of spinal microglia and revealed analgesic effects. Together, these data indicated that inhibition of stress-induced GR activation attenuated the preoperative anxiety-induced exacerbation of postoperative pain, and the suppression of spinal microglia activation may underlie this anti-hyperalgesia effect. Pending further studies, these findings suggested that GR and spinal microglia may play important roles in the development of preoperative anxiety-induced postoperative hyperalgesia and may serve as novel targets to prevent this phenomenon.

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Expression Profiling of Genes Modulated by Minocycline in a Rat Model of Neuropathic Pain

Cited by 37 publications

References 84 publications

Transcriptomic characterisation of the optimised rat model of Walker 256 breast cancer cell‐induced bone pain

Transcriptomic characterisation of the optimised rat model of Walker 256 breast cancer cell‐induced bone pain

Potentiation of Amitriptyline Anti-Hyperalgesic-Like Action By Astroglial Connexin 43 Inhibition in Neuropathic Rats

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

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