scholarly journals The terpenes camphene and alpha-bisabolol inhibit inflammatory and neuropathic pain via Cav3.2 T-type calcium channels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Vinicius M. Gadotti ◽  
Sun Huang ◽  
Gerald W. Zamponi
Keyword(s):  
Neuropathic Pain ◽  
Calcium Channels ◽  
Wide Spectrum ◽  
Thermal Hyperalgesia ◽  
Significant Inhibition ◽  
Dorsal Root Ganglion Neurons ◽  
Intraplantar Injection ◽  
Mouse Dorsal Root Ganglion ◽  
Ganglion Neurons ◽  
Micromolar Range

AbstractT-type calcium channels are known molecular targets of certain phytocannabinoids and endocannabinoids. Here we explored the modulation of Cav3.2 T-type calcium channels by terpenes derived from cannabis plants. A screen of eight commercially available terpenes revealed that camphene and alpha-bisabolol mediated partial, but significant inhibition of Cav3.2 channels expressed in tsA-201 cells, as well as native T-type channels in mouse dorsal root ganglion neurons. Both compounds inhibited peak current amplitude with IC50s in the low micromolar range, and mediated an additional small hyperpolarizing shift in half-inactivation voltage. When delivered intrathecally, both terpenes inhibited nocifensive responses in mice that had received an intraplantar injection of formalin, with alpha-bisabolol showing greater efficacy. Both terpenes reduced thermal hyperalgesia in mice injected with Complete Freund’s adjuvant. This effect was independent of sex, and absent in Cav3.2 null mice, indicating that these compounds mediate their analgesic properties by acting on Cav3.2 channels. Both compounds also inhibited mechanical hypersensitivity in a mouse model of neuropathic pain. Hence, camphene and alpha-bisabolol have a wide spectrum of analgesic action by virtue of inhibiting Cav3.2 T-type calcium channels.

scholarly journals Positive Regulatory Domain I–binding Factor 1 Mediates Peripheral Nerve Injury–induced Nociception in Mice by Repressing Kv4.3 Channel Expression

2020 ◽  
Author(s):  
Cunjin Wang ◽  
Yuchen Pan ◽  
Wenwen Zhang ◽  
Ying Chen ◽  
Chuhan Li ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Dorsal Root ◽  
Thermal Hyperalgesia ◽  
Dorsal Root Ganglion Neurons ◽  
Channel Expression ◽  
Mouse Dorsal Root Ganglion ◽  
Ganglion Neurons

Background The transcriptional repressor positive regulatory domain I–binding factor 1 (PRDM1) is expressed in adult mouse dorsal root ganglion and regulates the formation and function of peripheral sensory neurons. The authors hypothesized that PRDM1 in the dorsal root ganglion may contribute to peripheral nerve injury–induced nociception regulation and that its mechanism may involve Kv4.3 channel transcriptional repression. Methods Nociception was induced in C57BL/6 mice by applying chronic constriction injury, complete Freund’s adjuvant, or capsaicin plantar injection. Nociceptive response was evaluated by mechanical allodynia, thermal hyperalgesia, cold hyperalgesia, or gait analysis. The role of PRDM1 was evaluated by injection of Prdm1 knockdown and overexpression adeno-associated viruses. The interaction of PRDM1 at the Kv4.3 (Kcnd3) promoter was evaluated by chromatin immunoprecipitation assay. Excitability of dorsal root ganglion neurons was evaluated by whole cell patch clamp recordings, and calcium signaling in spinal dorsal horn neurons was evaluated by in vivo two-photon imaging. Results Peripheral nerve injury increased PRDM1 expression in the dorsal root ganglion, which reduced the activity of the Kv4.3 promoter and repressed Kv4.3 channel expression (injured vs. uninjured; all P < 0.001). Knockdown of PRDM1 rescued Kv4.3 expression, reduced the high excitability of injured dorsal root ganglion neurons, and alleviated peripheral nerve injury–induced nociception (short hairpin RNA vs. Scram; all P < 0.05). In contrast, PRDM1 overexpression in naive mouse dorsal root ganglion neurons diminished Kv4.3 channel expression and induced hyperalgesia (PRDM1 overexpression vs. control, mean ± SD; n = 13; all P < 0.0001) as evaluated by mechanical allodynia (0.6 ± 0.3 vs. 1.2 ± 0.2 g), thermal hyperalgesia (5.2 ± 1.3 vs. 9.8 ± 1.7 s), and cold hyperalgesia (3.4 ± 0.5 vs. 5.3 ± 0.6 s). Finally, PRDM1 downregulation in naive mice reduced the calcium signaling response of spinal dorsal horn neurons to thermal stimulation. Conclusions PRDM1 contributes to peripheral nerve injury–induced nociception by repressing Kv4.3 channel expression in injured dorsal root ganglion neurons. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Expression and Regulation of Cav3.2 T-Type Calcium Channels during Inflammatory Hyperalgesia in Mouse Dorsal Root Ganglion Neurons

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0127572 ◽  
Author(s):  
Masaya Watanabe ◽  
Takashi Ueda ◽  
Yasuhiro Shibata ◽  
Natsuko Kumamoto ◽  
Shoichi Shimada ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Calcium Channels ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Inflammatory Hyperalgesia ◽  
Mouse Dorsal Root Ganglion ◽  
Ganglion Neurons

NMDA Antagonist Peptide Supplementation Enhances Pain Alleviation by Adrenal Medullary Transplants

2005 ◽  
Vol 14 (4) ◽  
pp. 203-211 ◽  
Author(s):  
Farinaz Nasirinezhad ◽  
Jacqueline Sagen
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Striated Muscle ◽  
Thermal Hyperalgesia ◽  
Nmda Antagonist ◽  
Nmda Receptor Antagonist ◽  
Intraplantar Injection ◽  
Amino Acid Peptide ◽  
Spinal Subarachnoid Space ◽  
Pain Symptoms

Spinal transplantation of adrenal medullary chromaffin cells has been shown to decrease pain responses in several animal models. Improved potency may be possible by engineering cells to produce greater levels of naturally derived analgesics. As an initial screen for potential candidates, adrenal medullary transplants were evaluated in combination with exogenously administered neuropeptides in rodent pain models. Histogranin is a 15-amino acid peptide that exhibits NMDA receptor antagonist activity. The stable derivative [Ser1]histogranin (SHG) can attenuate pain symptoms in some animal models. The formalin model for neurogenic inflammatory pain and the chronic constriction injury (CCI) model for neuropathic pain were used to evaluate the combined effects of chromaffin cell transplantation and intrathecal (IT) SHG injections. Animals were implanted with either adrenal medullary or control striated muscle tissue in the spinal subarachnoid space. For evaluation of formalin responses, animals were pretreated with SHG (0.5, 1.0, 3.0 μg) followed by an intraplantar injection of formalin, and flinching responses were quantified. Pretreatment with SHG had no significant effect on flinching behavior in control animals at lower doses, with incomplete attenuation only at the highest dose. In contrast, 0.5 μg SHG significantly reduced flinching responses in animals with adrenal medullary transplants, and 1.0 μg nearly completely eliminated flinching in these animals in the tonic phase. For evaluation of effects on neuropathic pain, animals received transplants 1 week following CCI, and were tested for thermal and mechanical hyperalgesia and cold allodynia before and following SHG treatment. The addition of low doses of SHG nearly completely eliminated neuropathic pain symptoms in adrenal medullary transplanted animals, while in control transplanted animals only thermal hyperalgesia was attenuated, at the highest dose of SHG. These results suggest that SHG can augment adrenal medullary transplants, and the combination may result in improved effectiveness and range in the treatment of chronic pain syndromes.

G-proteins are involved in riluzole inhibition of high voltage-activated calcium channels in rat dorsal root ganglion neurons

1997 ◽  
Vol 762 (1-2) ◽  
pp. 235-239 ◽  
Author(s):  
Chao-Sheng Huang ◽  
Jin-Ho Song ◽  
Keiichi Nagata ◽  
Dennis Twombly ◽  
Jay Z Yeh ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Calcium Channels ◽  
G Proteins ◽  
High Voltage ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Ganglion Neurons
Sign in / Sign up

Export Citation Format

Share Document