scholarly journals The Role of the Capsaicin 8 % Patch (Qutenza®) in the Treatment of Post-herpetic Neuralgia

US Neurology ◽  
2015 ◽  
Vol 11 (01) ◽  
pp. 34
Author(s):  
Gordon Irving ◽  
Keyword(s):  
Transient Receptor Potential ◽  
Rating Scale ◽  
Topical Therapy ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Transient Receptor Potential Vanilloid ◽  
Post Herpetic Neuralgia ◽  
Local Cooling ◽  
Patch Application ◽  
Dermal Patch

Post-herpetic neuralgia (PHN) occurs as a complication of acute herpes zoster. The capsaicin 8 % (w/w) dermal patch (Qutenza®) is a transient receptor potential vanilloid agonist that increases intracellular calcium concentration, triggering calcium-dependent protease enzymes to cause cytoskeletal breakdown. This action is thought to lead to loss of cellular integrity and defunctionalization of nociceptor epidermal nerve fibers. The capsaicin 8 % patch is indicated in the US for the treatment of neuropathic pain associated with PHN. In pivotal, randomized, doubleblind, multicenter trials in patients with PHN, a single 60-minute application of the capsaicin 8 % dermal patch reduced mean numeric pain rating scale scores between baseline and weeks 2–8 to a significantly greater extent than the low-dose comparator patch (capsaicin 0.04 % w/w). The capsaicin 8 % (w/w) dermal patch was found to be safe and generally well-tolerated. Most commonly reported side effects were local, comprising dermal irritation, erythema, and pain at the site of application. These effects were transient and mild to moderate in severity. Transient patch application-related pain was not a barrier to use and was managed with local cooling or oral analgesics in nearly all cases. Thus, the capsaicin 8 % dermal patch appears to have a good safety profile, is well tolerated, and offers effective topical therapy in some patients with PHN. This review aims to characterize the use of the capsaicin 8 % dermal patch in the treatment of PHN.

scholarly journals Ablation of TRPV1 Abolishes Salicylate-Induced Sympathetic Activity Suppression and Exacerbates Salicylate-Induced Renal Dysfunction in Diet-Induced Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1234
Author(s):  
Beihua Zhong ◽  
Shuangtao Ma ◽  
Donna H. Wang
Keyword(s):  
Renal Dysfunction ◽  
Transient Receptor Potential ◽  
Kidney Injury ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Diabetic Patients ◽  
Transient Receptor Potential Vanilloid ◽  
Renal Nerve ◽  
Urine Albumin ◽  
Trpv1 Channels

Sodium salicylate (SA), a cyclooxygenase inhibitor, has been shown to increase insulin sensitivity and to suppress inflammation in obese patients and animal models. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed in afferent nerve fibers. Cyclooxygenase-derived prostaglandins are involved in the activation and sensitization of TRPV1. This study tested whether the metabolic and renal effects of SA were mediated by the TRPV1 channel. Wild-type (WT) and TRPV1−/− mice were fed a Western diet (WD) for 4 months and received SA infusion (120mg/kg/day) or vehicle for the last 4 weeks of WD feeding. SA treatment significantly increased blood pressure in WD-fed TRPV1−/− mice (p < 0.05) but not in WD-fed WT mice. Similarly, SA impaired renal blood flow in TRPV1−/− mice (p < 0.05) but not in WT mice. SA improved insulin and glucose tolerance in both WT and TRPV1−/− mice on WD (all p < 0.05). In addition, SA reduced renal p65 and urinary prostaglandin E2, prostaglandin F1α, and interleukin-6 in both WT and TRPV1−/− mice (all p < 0.05). SA decreased urine noradrenaline levels, increased afferent renal nerve activity, and improved baroreflex sensitivity in WT mice (all p < 0.05) but not in TRPV1−/− mice. Importantly, SA increased serum creatinine and urine kidney injury molecule-1 levels and decreased the glomerular filtration rate in obese WT mice (all p < 0.05), and these detrimental effects were significantly exacerbated in obese TRPV1−/− mice (all p < 0.05). Lastly, SA treatment increased urine albumin levels in TRPV1−/− mice (p < 0.05) but not in WT mice. Taken together, SA-elicited metabolic benefits and anti-inflammatory effects are independent of TRPV1, while SA-induced sympathetic suppression is dependent on TRPV1 channels. SA-induced renal dysfunction is dependent on intact TRPV1 channels. These findings suggest that SA needs to be cautiously used in patients with obesity or diabetes, as SA-induced renal dysfunction may be exacerbated due to impaired TRPV1 in obese and diabetic patients.

Corydalis saxicola Alkaloids Attenuate Cisplatin-Induced Neuropathic Pain by Reducing Loss of IENF and Blocking TRPV1 Activation

2020 ◽  
Vol 48 (02) ◽  
pp. 407-428 ◽  
Author(s):  
Cui-Ping Kuai ◽  
Lin-Jie Ju ◽  
Pei-Pei Hu ◽  
Fang Huang
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Transient Receptor Potential ◽  
Life Quality ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Transient Receptor Potential Vanilloid ◽  
Therapeutic Effects ◽  
Necrosis Factor Alpha ◽  
Total Alkaloids

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of cisplatin, which is characterized by intolerable paresthesia, burning, and hyperalgesia, and severely impacts the life quality of patients. However, no clearly potent drug has been found for clinical medication due to its undefined mechanism. Corydalis Saxicola Bunting, a traditional Chinese medicine, has been proven to work well in anti-inflammation, blood circulations improvement, hemostasis, and analgesia. This study was designed to observe the effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cisplatin-induced neuropathic pain and to explore its potential mechanisms. In this study, the rats received intraperitoneal injection of 2[Formula: see text]mg/kg cisplatin twice a week for five weeks. Meanwhile, oral administration of low (30[Formula: see text]mg/kg)-, medium (60[Formula: see text]mg/kg)- and high (120[Formula: see text]mg/kg)-dose CSBTA were given daily for five weeks. By using Von-frey hair, heat radiant and [Formula: see text]C cold acetone, we found that CSBTA could obviously relieve cisplatin-induced mechanical, heat, and cold hyperalgesia. It has been verified that cisplatin-induced peripheral neuropathy is related to intraepidermal nerve fibers loss and activation of inflammation downstream. Our research found that Tumor necrosis factor-alpha (TNF-[Formula: see text]), Interleukin-1beta (IL-1[Formula: see text]), and Prostaglandin E2 (PGE2) were significantly increased by 10 intraperitoneal injections of cisplatin, and such pro-inflammation cytokines could be reduced via CSBTA administration. Besides, in the cisplatin model group, the neuronal structures of dorsal root ganglia (DRG) were severely damaged and the loss of intraepidermal nerve fibers occurred; but in the CSBTA administration groups, all above pathological changes were improved. Moreover, CSBTA could normalize the overexpression levels of p-p38 and Transient receptor potential vanilloid receptor (TRPV1) induced by cisplatin in DRG, trigeminal ganglion (TG), spinal cord, and foot of rats. In summary, we considered that CSBTA exerted its therapeutic effects by ameliorating neuronal damages, improving intraepidermal nerve fiber (IENF) loss, and inhibiting inflammation-induced p38 phosphorylation to block TRPV1 activation. These findings were the first to confirm the analgesic effect of CSBTA on CIPN and suggested a novel strategy for treating CIPN in clinic.

TRPV1 gene knockout impairs preconditioning protection against myocardial injury in isolated perfused hearts in mice

2007 ◽  
Vol 293 (3) ◽  
pp. H1791-H1798 ◽  
Author(s):  
Beihua Zhong ◽  
Donna H. Wang
Keyword(s):  
Substance P ◽  
Receptor Antagonist ◽  
Transient Receptor Potential ◽  
Diastolic Pressure ◽  
Gene Knockout ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Left Ventricular ◽  
Transient Receptor Potential Vanilloid ◽  
Beneficial Effects

Although the transient receptor potential vanilloid type 1 (TRPV1)-containing afferent nerve fibers are widely distributed in the heart, the relationship between TRPV1 function and cardiac ischemic preconditioning (PC) has not been well defined. Using TRPV1 knockout mice (TRPV1−/−), we studied the role of TRPV1 in PC-induced myocardial protection. Hearts of gene-targeted TRPV1-null mutant (TRPV1−/−) or wild-type (WT) mice were Langendorffly perfused in the presence or absence of CGRP8-37, a selective calcitonin gene-related peptide (CGRP) receptor antagonist; or RP-67580, a selective neurokinin-1 receptor antagonist when hearts were subjected to three 5-min periods of ischemia PC followed by 30 min of global ischemia and 40 min of reperfusion (I/R). PC before I/R decreased left ventricular (LV) end-diastolic pressure and increased LV developed pressure, coronary flow (CF), peak-positive maximum rate of rise of LV pressure in WT mice (PC-WT) compared with PC-TRPV1−/−, TRPV1−/−, or WT hearts ( P < 0.05), and PC also decreased LV end-diastolic pressure in PC-TRPV1−/− compared with TRPV1−/−. CGRP8-37 or RP-67580 abolished PC-induced protection in WT but not TRPV1−/− hearts ( P < 0.05). Moreover, PC decreased lactate dehydrogenase release and infarct size in PC-WT compared with PC-TRPV1−/−, TRPV1−/−, or WT hearts, and it also lowered these parameters in PC-TRPV1−/− compared with TRPV1−/− hearts ( P < 0.05). Radioimmunoassay showed that the release of substance P and CGRP after PC was higher in WT hearts than in TRPV1−/− hearts ( P < 0.05), which was attenuated by capsazepine in WT but not TRPV1−/− hearts. Thus PC-induced protection of the heart was impaired in TRPV1−/− hearts, indicating that TRPV1 contributes to the beneficial effects of preconditioning against I/R injury through release substance P and CGRP.

scholarly journals Skin Matters: Identifying Pain Mechanisms and Predicting Treatment Outcomes

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Edward A. Shipton
Keyword(s):  
Treatment Outcomes ◽  
Transient Receptor Potential ◽  
Pain Syndrome ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Transient Receptor Potential Vanilloid ◽  
Pain Mechanisms ◽  
Small Fiber ◽  
Voltage Gated Sodium Channels ◽  
Sensor Proteins

The skin acts as a complex sensory organ. The emerging new data on peripheral pain mechanisms from within the skin is presented. This data has led to new insights into the potential pain mechanisms for various pain conditions including neuropathic pain (from small fiber neuropathies) and Complex Regional Pain Syndrome. The somatosensory neurons that innervate our skin constantly update our brains on the objects and environmental factors that surround us. Cutaneous sensory neurons expressing nociceptive receptors such as transient receptor potential vanilloid 1 channels and voltage-gated sodium channels are critical for pain transmission. Epidermal cells (such as keratinocytes, Langerhans cells, and Merkel cells) express sensor proteins and neuropeptides; these regulate the neuroimmunocutaneous system and participate in nociception and neurogenic inflammation. In the past two decades, there has been widespread use of modalities such as punch skin biopsies, quantitative sensory testing, and laser-evoked potentials to evaluate small caliber nerve fibers. This paper explores these laboratory techniques as well as the phenomenon of small fiber neuropathy. Treatment using transdermal drug delivery is discussed. There is potential for these findings to predict treatment outcomes in clinical practice and to develop new therapies for different pain conditions. These findings should enhance the physician's ability to evaluate and treat diverse types of pain.

scholarly journals Role of transient receptor potential vanilloid 1 in the modulation of airway smooth muscle tone and calcium handling

2017 ◽  
Vol 312 (6) ◽  
pp. L812-L821 ◽  
Author(s):  
Gene T. Yocum ◽  
Jun Chen ◽  
Christine H. Choi ◽  
Elizabeth A. Townsend ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Calcium Oscillations ◽  
Transient Receptor Potential Vanilloid ◽  
Organ Bath ◽  
Transient Receptor

Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel expressed on airway nerve fibers that modulates afferent signals, resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+-ATPase-2. In guinea pig tracheal ring organ bath experiments, the TRPV1 agonist capsaicin led to ASM contraction, but this contraction was significantly attenuated by the sodium channel inhibitor bupivacaine ( n = 4, P < 0.05) and the neurokinin-2 receptor antagonist GR-159897 ( n = 4, P < 0.05), suggesting that this contraction is neutrally mediated. However, pretreatment of guinea pig and human ASM in organ bath experiments with the TRPV1 antagonist capsazepine inhibited the maintenance phase of an acetylcholine-induced contraction ( n = 4, P < 0.01 for both species). Similarly, capsazepine inhibited methacholine-induced contraction of peripheral airways in mouse precision-cut lung slice (PCLS) experiments ( n = 4–5, P < 0.05). Although capsazepine did not inhibit store-operated calcium entry in mouse ASM cells in PCLS ( n = 4–7, P = nonsignificant), it did inhibit calcium oscillations ( n = 3, P < 0.001). These studies suggest that TRPV1 is expressed on ASM, including the SR, but that ASM TRPV1 activation does not play a significant role in initiation of ASM contraction. However, capsazepine does inhibit maintenance of contraction, likely by inhibiting calcium oscillations.

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