Editorial

Jump to: Research, Review

3 pages, 190 KiB

Open AccessEditorial

Things Able to Treat Pain

by Anna Maria Aloisi

Int. J. Mol. Sci. 2023, 24(12), 10346; https://doi.org/10.3390/ijms241210346 - 19 Jun 2023

Viewed by 727

Abstract

Chronic pain is a medical condition that affects a considerable number of people of all ages [...] Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

Research

Jump to: Editorial, Review

18 pages, 31793 KiB

Open AccessArticle

Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats

by David Á. Karádi, Anna Rita Galambos, Péter P. Lakatos, Joost Apenberg, Sarah K. Abbood, Mihály Balogh, Kornél Király, Pál Riba, Nariman Essmat, Edina Szűcs, Sándor Benyhe, Zoltán V. Varga, Éva Szökő, Tamás Tábi and Mahmoud Al-Khrasani

Int. J. Mol. Sci. 2023, 24(9), 7970; https://doi.org/10.3390/ijms24097970 - 27 Apr 2023

Cited by 2 | Viewed by 2309

Abstract

Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, [...] Read more.

Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, and particularly their combination with morphine on rat mononeuropathic pain following acute or chronic oral administration. The impact of telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic animals were assessed by [³⁵S]GTPγS-binding assay. Finally, the glutamate content of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment study, the combination of subanalgesic doses of telmisartan and morphine ameliorated allodynia and resulted in a leftward shift in the dose–response curve of morphine in the [³⁵S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed morphine analgesic-tolerance development. Our study has identified a promising combination therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze the effect of each component. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Graphical abstract

11 pages, 1533 KiB

Open AccessArticle

Effects of Intracerebroventricular and Intra-Arcuate Nucleus Injection of Ghrelin on Pain Behavioral Responses and Met-Enkephalin and β-Endorphin Concentrations in the Periaqueductal Gray Area in Rats

by Samaneh Pirzadeh, Javad Sajedianfard, Anna Maria Aloisi and Mahboobeh Ashrafi

Int. J. Mol. Sci. 2019, 20(10), 2475; https://doi.org/10.3390/ijms20102475 - 19 May 2019

Cited by 8 | Viewed by 4290

Abstract

Ghrelin is an endogenous ligand for orphan growth hormone secretagogue receptors. Ghrelin receptors have been found in central nervous system (CNS) areas responsible for pain modulation and transmission. This study investigated the effects of intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin [...] Read more.

Ghrelin is an endogenous ligand for orphan growth hormone secretagogue receptors. Ghrelin receptors have been found in central nervous system (CNS) areas responsible for pain modulation and transmission. This study investigated the effects of intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin on pain behavioral responses and levels of β-endorphin (β-EP) and met-enkephalin (MENK) in the periaqueductal gray area (PAG) during the formalin test in rats. Thirty-five male rats were studied in five groups. Ghrelin was injected into the left lateral ventricle (ICV, 5 µL) or into the ARC (1 µL). After 15 min, formalin (2.5%) was subcutaneously injected into the left hind paw. Behavioral nociceptive scores were recorded for 60 min. MENK and β-EP were collected by microdialysis in the PAG and determined by high-performance liquid chromatography (HPLC). ICV and ARC injection of ghrelin significantly reduced pain in all phases of the formalin test (p < 0.001). Dialysate concentrations of MENK and β-EP in the PAG increased in all the phases (p < 0.01). In conclusion, the present study shows that the ARC nucleus and the endogenous opioid system are involved in ghrelin-induced pain modulation. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Figure 1

17 pages, 3452 KiB

Open AccessArticle

Modulation of SUR1 K_ATP Channel Subunit Activity in the Peripheral Nervous System Reduces Mechanical Hyperalgesia after Nerve Injury in Mice

by Wing Luu, James Bjork, Erin Salo, Nicole Entenmann, Taylor Jurgenson, Cole Fisher and Amanda H. Klein

Int. J. Mol. Sci. 2019, 20(9), 2251; https://doi.org/10.3390/ijms20092251 - 07 May 2019

Cited by 22 | Viewed by 3635

Abstract

The ATP-sensitive K⁺ channel (K_ATP) is involved in hypersensitivity during chronic pain and is presumed to be a downstream target of mu opioid receptors. Multiple subtypes of K_ATP channels exist in the peripheral and central nervous system and their [...] Read more.

The ATP-sensitive K⁺ channel (K_ATP) is involved in hypersensitivity during chronic pain and is presumed to be a downstream target of mu opioid receptors. Multiple subtypes of K_ATP channels exist in the peripheral and central nervous system and their activity may be inversely correlated to chronic pain phenotypes in rodents. In this study, we investigated the different K_ATP channel subunits that could be involved in neuropathic pain in mice. In chronic pain models utilizing spinal nerve ligation, SUR1 and Kir6.2 subunits were found to be significantly downregulated in dorsal root ganglia and the spinal cord. Local or intrathecal administration of SUR1-K_ATP channel subtype agonists resulted in analgesia after spinal nerve ligation but not SUR2 agonists. In ex-vivo nerve recordings, administration of the SUR1 agonist diazoxide to peripheral nerve terminals decreased mechanically evoked potentials. Genetic knockdown of SUR1 through an associated adenoviral strategy resulted in mechanical hyperalgesia but not thermal hyperalgesia compared to control mice. Behavioral data from neuropathic mice indicate that local reductions in SUR1-subtype K_ATP channel activity can exacerbate neuropathic pain symptoms. Since neuropathic pain is of major clinical relevance, potassium channels present a target for analgesic therapies, especially since they are expressed in nociceptors and could play an essential role in regulating the excitability of neurons involved in pain-transmission. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Figure 1

9 pages, 891 KiB

Open AccessArticle

L-Lysine as the Molecule Influencing Selective Brain Activity in Pain-Induced Behavior of Rats

by Liudmila A. Severyanova, Victor A. Lazarenko, Dmitry V. Plotnikov, Maxim E. Dolgintsev and Alexey A. Kriukov

Int. J. Mol. Sci. 2019, 20(8), 1899; https://doi.org/10.3390/ijms20081899 - 17 Apr 2019

Cited by 11 | Viewed by 4209

Abstract

Lysine-rich proteins are some of the most important proteins of neurons and it has become necessary to investigate the possible role of L-lysine as a brain functioning regulator. The purpose of our study is to identify the characteristics and the mechanisms of L-lysine [...] Read more.

Lysine-rich proteins are some of the most important proteins of neurons and it has become necessary to investigate the possible role of L-lysine as a brain functioning regulator. The purpose of our study is to identify the characteristics and the mechanisms of L-lysine effects on the different types of pain-induced behavior in the stimulation of tail and foot-shock models in 210 adult male Wistar rats. L-lysine was administered in intraperitoneal or intracerebroventricular injections in doses of 0.15–50.0 µg/kg. When a tail is irritated, L-lysine was found to enhance pain sensitivity and affective defense after both intraperitoneal and intracerebroventricular administration. In the case of unavoidable painful irritation of a pair of rats with both types of L-lysine administration, there was no direct correlation of the severity of pain with defensive reactions and outbursts of aggression. This indicates a more complex integration of the activity of brain structures in this situation of animal interaction, which was confirmed by the results of the direct amino acid action on the periventricular brain structures. Our findings show that L-lysine influences the selective brain activity in dependence on the biological significance of pain-induced behavior. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Figure 1

12 pages, 1746 KiB

Open AccessArticle

The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice

by Daxian Li, Ji Hwan Lee, Chang Won Choi, Jaihwan Kim, Sun Kwang Kim and Woojin Kim

Int. J. Mol. Sci. 2019, 20(7), 1652; https://doi.org/10.3390/ijms20071652 - 03 Apr 2019

Cited by 19 | Viewed by 3728

Abstract

The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used [...] Read more.

The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α₂-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α₁-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT₃ receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT_{1, 2} receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α₂-adrenergic receptor, and both α₂-adrenergic and 5-HT₃ receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Figure 1

7 pages, 895 KiB

Open AccessCommunication

Sex Differences in a Rodent Model of HIV-1-Associated Neuropathic Pain

by Josée Guindon, Henry Blanton, Seth Brauman, Kelsey Donckels, Madhusudhanan Narasimhan and Khalid Benamar

Int. J. Mol. Sci. 2019, 20(5), 1196; https://doi.org/10.3390/ijms20051196 - 09 Mar 2019

Cited by 25 | Viewed by 3569

Abstract

Worldwide, women account for approximately 51% of human immunodeficiency virus-1 (HIV) seropositive individuals. The prevalence of neuropathic pain among individuals with HIV and a lack of preclinical data characterizing sex differences prompted us to address this knowledge gap. C57BL/6 male and female mice [...] Read more.

Worldwide, women account for approximately 51% of human immunodeficiency virus-1 (HIV) seropositive individuals. The prevalence of neuropathic pain among individuals with HIV and a lack of preclinical data characterizing sex differences prompted us to address this knowledge gap. C57BL/6 male and female mice received multiple intrathecal injections of HIV-glycoprotein 120 (gp120), followed by determination of mechanical allodynia and thermal hypersensitivity for four weeks. The influence of ovarian hormones in the gp120 pain model was evaluated by comparison of ovariectomized (OVX) mice versus sham control. We found that gp120-induced neuropathic pain-like behaviors are sex-dependent. Female mice showed both increased mechanical allodynia and increased cold sensitivity relative to their male counterparts. The OVX mice showed reduced pain sensitivity compared to sham, suggesting a role of the ovarian hormones in sex differences in pain sensitivity to gp120. Gp120-induced neuropathic pain caused a shift in estrous cycle toward the estrus phase. However, there is a lack of clear correlation between the estrous cycle and the development of neuropathic pain-like behaviors during the four week recording period. This data provided the first evidence for sex differences in a rodent model of HIV-related neuropathic pain, along with a potential role of ovarian hormones. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

29 pages, 3393 KiB

Open AccessReview

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy

by Renata Zajączkowska, Magdalena Kocot-Kępska, Wojciech Leppert, Anna Wrzosek, Joanna Mika and Jerzy Wordliczek

Int. J. Mol. Sci. 2019, 20(6), 1451; https://doi.org/10.3390/ijms20061451 - 22 Mar 2019

Cited by 400 | Viewed by 21332

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited. There are six main substance groups that cause damage to peripheral sensory, motor and autonomic neurons, which result in the development of CIPN: platinum-based antineoplastic agents, vinca alkaloids, epothilones (ixabepilone), taxanes, proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). Among them, the most neurotoxic are platinum-based agents, taxanes, ixabepilone and thalidomide; other less neurotoxic but also commonly used drugs are bortezomib and vinca alkaloids. This paper reviews the clinical picture of CIPN and the neurotoxicity mechanisms of the most common antineoplastic agents. A better understanding of the risk factors and underlying mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pain)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Molecular Mechanisms of Pain

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI