Role of Sigma-1 Receptors in Paclitaxel-Induced Neuropathic Pain in Mice

Nieto, Francisco R.; Cendán, Cruz Miguel; Sánchez-Fernández, Cristina; Cobos, Enrique J.; Entrena, José Manuel; Tejada, Miguel; Zamanillo, Daniel; Vela, José Miguel; Baeyens, José M.

doi:10.1016/j.jpain.2012.08.006

Cited by 111 publications

(132 citation statements)

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“…These antinociceptive effects are in good agreement with previous data related to the effect of σ1R antagonists in different animal models such as the sciatic nerve ligation (de la Puente et al., 2009; Romero et al., 2012) or the paclitaxel‐induced neuropathy (Nieto et al., 2012). …”

Section: Discussionmentioning

confidence: 99%

“…The concentration of the solutions was adjusted to inject a volume of 0.5 mL. Doses were selected from pilot experiments from our laboratory using Wistar rats (data not shown) and are in agreement with published data (Nieto et al., 2012). Phenylephrine and carbachol were obtained from Sigma (Sigma Chemical Company, Poole, UK) and were dissolved in distilled water.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, recent studies using σ1R knock‐out mice and pharmacological interventions with selective σ1R antagonists (Romero et al., 2012) showed an antinociceptive effect of σ1R modulation independent of the opioid system. σ1R knock‐out mice showed attenuated nociceptive responses in the formalin test (Cendán et al., 2005), in sciatic nerve injury (de la Puente et al., 2009), in capsaicin sensitization (Entrena et al., 2009) and in antitumoral‐induced cold and mechanical allodynia (Nieto et al., 2012). …”

Section: Introductionmentioning

confidence: 99%

“…As σ1R antagonists are effective in several peripheral neuropathy models, including sciatic nerve ligation (de la Puente et al., 2009; Romero et al., 2012) and paclitaxel‐induced neuropathy (Nieto et al., 2012), our aim was to test if the blockade of the σ1R with E‐52862 may modify the signs of neuropathy in Zucker diabetic fatty (ZDF) rats, a widely accepted model of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Paniagua

Girón

Goicoechea

et al. 2016

European Journal of Pain

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BackgroundE‐52862 (S1RA, 4‐[2‐[[5‐methyl‐1‐(2‐naphthalenyl)‐1H‐pyrazol‐3‐yl]oxy]ethyl]‐morpholine), a novel selective sigma 1 receptor (σ1R) antagonist, has demonstrated efficacy in nociceptive and neuropathic pain models. Our aim was to test if σ1R blockade with E‐52862 may modify the signs of neuropathy in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model.MethodsMechanical and thermal response thresholds were tested on 7‐, 13‐, 14‐ and 15‐week‐old ZDF rats treated with saline or with E‐52862 acutely administered on week 13, followed by sub‐chronic administration (14 days). Axonal peripheral activity (skin–saphenous nerve preparation) and isolated aorta or mesenteric bed reactivity were analysed in 15‐week‐old ZDF rats treated with saline or E‐52862 and in LEAN rats.ResultsZucker diabetic fatty rats showed significantly decreased thermal withdrawal latency and threshold to mechanical stimulation on week 13 compared to week 7 (prediabetes) and with LEAN animals; single‐dose and sub‐chronic E‐52862 administration restored both parameters to those recorded on week 7. Regarding axonal peripheral activity, E‐52862 treatment increased the mean mechanical threshold (77.3 ± 21 mN vs. 19.6 ± 1.5 mN, saline group) and reduced the response evoked by mechanical increasing stimulation (86.4 ± 36.5 vs. 352.8 ± 41.4 spikes) or by repeated mechanical supra‐threshold steps (39.4 ± 1.4 vs. 83.5 ± 0.9). E‐52862 treatment also restored contractile response to phenylephrine in aorta and mesenteric bed.ConclusionsE‐52862 administration reverses neuropathic (behavioural and electrophysiological) and vascular signs in the ZDF rat.SignificanceBlockade of σ1R avoids the development of diabetic neuropathy in rats, and may represent a potentially useful therapeutic approach to peripheral neuropathies in diabetic patients.What does this study add? This study presents evidences for the potential usefulness of sigma receptor blockade on diabetic neuropathy in rats.The methodology includes behavioural evidences, electrophysiological data and vascular‐isolated models.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Paniagua

Girón

Goicoechea

et al. 2016

European Journal of Pain

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“…Specifically, intrathecal injection of s1R antagonists, such as BD1047 (N-[2-(3,4-dichlorophenyl) ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) or S1RA, reduces painful behavior after peripheral nerve injury (Roh et al, 2008b;Romero et al, 2012), whereas s1R knockout mice reduce central sensitization and diminish hyperalgesic responses after injury (de la Puente et al, 2009). Additionally, blockade of s1R can prevent chemotherapy-induced neuropathic pain (Nieto et al, 2012). Finally, formalin-and capsaicininduced inflammation pain is attenuated by s1R knockout and by s1R antagonist administration (Cendan et al, 2005;Entrena et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

Pan

Guo

Kwok

et al. 2014

J Pharmacol Exp Ther

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Sigma-1 receptor (s1R), an endoplasmic reticulum-chaperone protein, can modulate painful response after peripheral nerve injury. We have demonstrated that voltage-gated calcium current is inhibited in axotomized sensory neurons. We examined whether s1R contributes to the sensory dysfunction of voltagegated calcium channel (VGCC) after peripheral nerve injury through electrophysiological approach in dissociated rat dorsal root ganglion (DRG) neurons. Animals received either skin incision (Control) or spinal nerve ligation (SNL). Both s1R agonists, (1)pentazocine (PTZ) and DTG [1,3-di-(2-tolyl)guanidine], dose dependently inhibited calcium current (I Ca ) with Ba 21 as charge carrier in control sensory neurons. The inhibitory effect of s1R agonists on I Ca was blocked by s1R antagonist, BD1063(1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine dihydrochloride) or BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide). PTZ and DTG showed similar effect on I Ca in axotomized fifth DRG neurons (SNL L5). Both PTZ and DTG shifted the voltage-dependent activation and steady-state inactivation of VGCC to the left and accelerated VGCC inactivation rate in both Control and axotomized L5 SNL DRG neurons. The s1R antagonist, BD1063 (10 mM), increases I Ca in SNL L5 neurons but had no effect on Control and noninjured fourth lumbar neurons in SNL rats. Together, the findings suggest that activation of sR1 decreases I Ca in sensory neurons and may play a pivotal role in pain generation.

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Sigma‐1 Receptor Expression in DRG Neurons During a Carrageenan‐Provoked Inflammation

Jerčić

Kostić

Uljević

et al. 2019

The Anatomical Record

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Sigma 1 receptor (σ1R) is a non-opioid receptor that modulates pain perception and is strongly expressed in dorsal root ganglion (DRG) neurons. We studied the changes in the expression of σ1R in different subpopulations of DRG neurons during the first 48 hr in a carrageenaninduced inflammation rat model, with σ1R being a possible base for the development of neuropathic pain after inflammation. Twenty Sprague Dawley rats were divided into five groups (N = 4 in each group): the control (C) group was sacrificed immediately; all other animals received an intraplantar injection of 0.1 mL 2% carrageenan and were sacrificed in 6, 12, 24 or 48 hr after the injection and DRGs were collected and processed for immunohistochemistry. σ1R fluorescence intensity decreased slightly but significantly in up to 24 hr post-carrageenan injection in all subpopulations of DRG neurons (ib4+; ib4− medium, ib4− large and ib4− in total; P < 0.05 -P < 0.001), with the exception of the ib4− small neurons (<25 μm; P > 0.05). This decrement was followed by a subsequent increase in σ1R fluorescence intensity 48 hr after the plantar carrageenan injection (P < 0.05 -P < 0.0001). The same trend was also observed in the CGRP+ population of the DRG neurons, in the total population as well as in the CGRP+ small (<25 μm) and larger CGRP (>25 μm) sub-populations (P < 0.05 -P < 0.001). The presented results may contribute to further understanding of role of σ1R in the development of peripheral sensitization during inflammation. They may also be valuable for the therapeutic application of σ1R antagonists, particularly in the adjustment of the ABBREVIATIONS: CCI = chronic constriction injury; CFA = complete Freund adjuvant; CGRP = calcitonin gene-related peptide; DRG = dorsal root ganglion; ER = endoplasmic reticulum; ib4 = isolectin B4; IP3 = inositol 1,4,5-triphosphate; KO = knockout; PBS = phosphate-buffered saline; SNL = spinal nerve ligation; σ1R = sigma 1 receptor Grant sponsor: Ministarstvo Znanosti, Obrazovanja i Sporta.

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Role of Sigma-1 Receptors in Paclitaxel-Induced Neuropathic Pain in Mice

Cited by 111 publications

References 55 publications

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons

Sigma‐1 Receptor Expression in DRG Neurons During a Carrageenan‐Provoked Inflammation

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Role of Sigma-1 Receptors in Paclitaxel-Induced Neuropathic Pain in Mice

Cited by 111 publications

References 55 publications

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Blockade of sigma 1 receptors alleviates sensory signs of diabetic neuropathy in rats

Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca2+ Current in Sensory Neurons

Sigma‐1 Receptor Expression in DRG Neurons During a Carrageenan‐Provoked Inflammation

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Sigma-1 Receptor Antagonism Restores Injury-Induced Decrease of Voltage-Gated Ca²⁺ Current in Sensory Neurons