FEATURED PAPERS

05/24/2022

Microglia-independent peripheral neuropathic pain

Neuropathic pain arises as a direct consequence of a lesion or disease of the somatosensory system. A hallmark of neuropathic pain is the proliferation, morphological changes and activation of microglia in the spinal dorsal horn. Salter and cols discovered a form of neuropathic pain that is independent of microglia. Nucleus pulposus secrete soluble factor which recruit macrophages into the sciatic nerve where they release BDNF which induce pain hypersensitivity. These findings help to explain the limited success of microglial inhibitors on neuropathic pain in human clinical trials.

Authors:

Tu, YuShan; Muley, Milind M.; Beggs, Simon; Salter, Michael W.

05/17/2022

Is it important to study pain in Parkinson’s disease?

Parkinson’s Disease (PD) has traditionally been considered a neurodegenerative disease with motor involvement associated with the accumulation and misfolding of the protein alpha-synuclein (aSyn). However, non-motor symptoms such as thermal and mechanical sensory dysfunction, as well as a considerable decrease in intraepidermal nerve fibers, are becoming more important in these patients; It remains unclear how aSyn misfolding could affect these symptoms.

Interestingly, when these researchers used an experimental model of this disease involving intramuscular injection of aSyn preformed fibrils (PFF), they found that aSyn is able to:

a) Spread from the PNS to the CNS by affecting sensory neuroanatomical connections

b) Cause neurodegeneration of sensory pathways

c) Associate with nociceptive hypersensitivity.

This represents a possibility of using aSyn transgenic models to understand molecular mechanisms related to pain in PD in the search for new therapeutics in the non-motor symptoms of these patients.

Authors:

Nelson Ferreira, Nádia Pereira Gonçalves, Asad Jan, Nanna Møller Jensen, Amelia van der Laan, Simin Mohseni, Christian Bjerggaard Vægter & Poul Henning Jensen.

05/10/2022

Emotional imbalances caused by chronic pain

It is well known that chronic pain states in humans may generate complex emotional imbalances. Many studies have shown that chronic pain indeed causes negative emotions and common pathologies, such as anxiety and depression. However, how chronic pain produces anxiety and depression at the brain level is unknown.

This work identified a specific neuronal circuit that explains, at least in part, how chronic pain alters the regulation of anxiety in the nervous system. Using a model of chronic neuropathic pain, Yamauchi and colleagues demonstrated that chronic pain dysregulates a group of GABAergic neurons in the stria terminalis (stria terminalis) of the brain, which subsequently affects neuronal activity in the lateral hypothalamus, generating anxiety.

These findings demonstrate that chronic pain induces synaptic plasticity changes on specific brain circuits, affecting the normal regulation of anxiety.

Authors:

Naoki Yamauchi, Keiichiro Sato, Kenta Sato, Shunsaku Murakawa, Yumi Hamasaki, Hiroshi Nomura, Taiju Amano and Masabumi Minami.

05/03/2022

A novel mechanism for chronic pain regulation

Chronic pain is a disease with limited treatments available, and it affects 32% of Chileans.

TRPV1 is a heat-sensitive membrane receptor that has been reported as involved in several models of heat pain, both chronic and acute.

According to the authors, the enzyme PDI (Protein Dithiol Isomerase) would be a novel participant in chronic pain regulation, activating TRPV1 allosterically (ligand-independent), which would lead to heat hyperalgesia (increase pain in response to noxious heat).

Authors:

Yongxue Zhang, Qi Miao, Sai Shi, Han Hao, Xinmeng Li, Zeyao Pu, Yakun Yang, Hailong An, Wei Zhang, Youzhen Kong, Xu Pang, Cunyang Gu, Nikita Gamper, Yi Wu, Hailin Zhang, Xiaona Du.

04/26/2022

GPR151 in nociceptors modulates neuropathic pain via regulating P2X3 function and microglial activation

In this study, authors demonstrated that GPR151 is highly expressed in dorsal root ganglion neurons (DRG). This receptor, coupled with the P2X3 ionic channels, modulates CSF1-induced microglial activation, which is essential for the initiation and maintenance of neuropathic pain. This data portray GPR151 and P2X3 as a promising therapeutic targets for this condition.

Authors:

Li-Ping Xia, Hao Luo, Qiang Ma, Ya-Kai Xie, Wei Li, Hailan Hu and Zhen-Zhong Xu

IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice

Are women at a greater risk for developing common chronic pain conditions?

A huge number of epidemiological studies demonstrate that chronic pain conditions are more common in women than in men. Women are also at a greater risk for developing common chronic pain conditions including migraines, low back pain, fibromyalgia, and irritable bowel syndrome.

They conclude that the sex dimorphism of capsaicin-evoked mechanical pain is promoted by estrogen in females and suppressed by androgen in males, implicating sex hormone homeostasis as a prerequisite for sex dimorphism in TRPV1-mediated mechanical pain.

The authors of this research recommend to rethink the way we design and analyze data for clinical trials for chronic pain treatment, as it is likely that medications will not work equally in males or females.

Authors:

Xin Luo, Ouyang Chen, Zilong Wang, Sangsu Bang, Jasmine Ji, Sang Hoon Lee, Yul Huh, Kenta Furutani, Qianru He, Xueshu Tao, Mei-Chuan Ko, Andrey Bortsov, Christopher R. Donnelly, Yong Chen, Andrea Nackley, Temugin Berta, Ru-Rong Ji

12/21/2021

Capsaicin-induced depolymerization of axonal microtubules mediates analgesia for trigeminal neuropathic pain

The article presents the investigation of nociceptors expressed in sensory neurons, specifically the TRPV1 ion channel. This protein is responsible for sensing temperature changes in the skin, specifically high temperatures that could cause tissue damage. However, this article presents the novel research that this channel could be activated by bacterial metabolites present in our system.

Featured Authors:

Chung S, Kim H, Kim D, Lee J M, Lee C J, Oh S B

12/13/2021

Combining topical agonists with the recording of event-related brain potentials to probe the functional involvement of TRPM8, TRPA1 and TRPV1 in heat and cold transduction in the human skin

TRP channels play a central role in the transduction of thermal and nociceptive stimuli by free nerve endings. Most of the research on these channels has been conducted in vitro or in vivo in non-human animals and translation of these results to humans must account for potential experimental biases and interspecific differences. This study aimed at evaluating the involvement of TRPM8 (Menthol), TRPA1 (Cinnamaldehyde) and TRPV1 (Capsaicin) channels in the transduction of heat and cold stimuli by the human thermonociceptive system.

Featured Authors:

Arthur S. Courtin & André Mouraux

11/06/2021

Association of Genetic Variant at Chromosome 12q23.1 With Neuropathic Pain Susceptibility

The ability to detect external noxious stimuli and signals from internal organs is essential to maintain physical integrity and homeostasis. This process is mediated by nociceptors, which recognize stimuli through specialized receptors. The perception of nociceptive pain depends on the continuity of the sensory fibers of the peripheral nerve, which is why functional humanized in vitro nerve models are coveted as an alternative to animal models due to their ease of access, lower cost, clinical relevance and the no need for recurring animal sacrifices. To this end, a sensory nerve model was developed using induced pluripotent stem cell (iPSC) derived nociceptors that are electrically active and exhibit a functional response to noxious stimuli.

Featured Authors:

Veluchamy A, Hébert HL, van Zuydam NR, Pearson ER, Campbell A, Hayward C, Meng W, McCarthy MI, Bennett DLH, Palmer CNA, Smith BH

11/29/2021

Capsaicin-induced depolymerization of axonal microtubules mediates analgesia for trigeminal neuropathic pain

This research suggests that capsaicin increases microtubule depolymerization, which induces axonal ablation and, therefore, mediates analgesia for neuropathic pain of the trigeminal nerve. To test their hypothesis, the researchers studied the effects of microtubule stabilization on capsaicin-induced axonal ablation, and analgesia for trigeminal neuropathic pain in mice.

Featured Authors:

Arora, Vipina; Li, Tingtinga; Kumari, Sinua; Wang, Shenga; Asgar, Jamilaa; Chung, Man-Kyoa

11/22/2021

3D culture platform of human iPSCs-derived nociceptors for peripheral nerve modelling and tissue innervation

TRP channels play a central role in the transduction of thermal and nociceptive stimuli by free nerve endings. Most of the research on these channels has been conducted in vitro or in vivo in non-human animals and translation of these results to humans must account for potential experimental biases and interspecific differences. This study aimed at evaluating the involvement of TRPM8 (Menthol), TRPA1 (Cinnamaldehyde) and TRPV1 (Capsaicin) channels in the transduction of heat and cold stimuli by the human thermonociceptive system.

Featured Authors:

Afonso Malheiro 1, Abhishek Harichandan 2, Joyce Bernardi 3, Adrián Seijas-Gamardo 1, Gonda F Konings 4, Paul G A Volders 3, Andrea Romano 4, Carlos Mota 5, Paul Wieringa 6, Lorenzo Moroni 7