Berberine Ameliorates Cold and Mechanical Allodynia in a Rat Model of Diabetic Neuropathy

Saha

Journal of Pharmacy and Pharmacology

et al. 2018

Objectives The role of nuclear factor‐2 erythroid related factor‐2 (Nrf2) activator, berberine (BBR), has been established in rat model of streptozotocin induced diabetic neuropathy. Around 30–40% of cancer patients, on paclitaxel (PTX) chemotherapy develop peripheral neuropathy. The present study was contemplated with the aim of establishing the neuropathy preventive role of BBR, in paclitaxel induced peripheral neuropathy model in rats. Methods A total of 30 Wistar rats were divided into five groups as follows: Group I: dimethyl sulfoxide; Group II: PTX+ 0.9% NaCl; Group III: Amitriptyline (ATL) + PTX; Group IV: BBR (10 mg/kg) + PTX and Group V: BBR (20 mg/kg) + PTX. Animals were assessed for tail flick latency, tail cold allodynia latency, histopathological scores, oxidative stress parameters, and mRNA expression of the Nrf2 gene in the sciatic nerve. Key findings Berberine significantly increased the tail flick and tail cold allodynia latencies and significantly decreased the histopathological score. BBR reduced oxidative stress by significantly decreasing the lipid peroxidation, increasing the superoxide dismutase and reduced glutathione levels in the sciatic nerve. BBR also increased the mRNA expression of Nrf2 gene in rat sciatic nerve. Conclusions All of these results showed the neuropathy preventing role of BBR in PTX induced neuropathy pain model in rats.

Section: Discussionsupporting

confidence: 72%

Study of nuclear factor-2 erythroid related factor-2 activator, berberine, in paclitaxel induced peripheral neuropathy pain model in rats

Saha

Journal of Pharmacy and Pharmacology

et al. 2018

“…This assay was reported almost two decades ago 42 and has since been used as originally described or with variations. 44, 46, 47, 70, 84, 86, 87, 93 On each of the testing days, animals were brought into the testing room for 1 hr in order to acclimate them to the environment. The room temperature was kept at 24 ± 1°C.…”

Section: Methodsmentioning

confidence: 99%

Sustained Morphine Administration Induces TRPM8-Dependent Cold Hyperalgesia

Gong

Jasmin

2017

The Journal of Pain

It is not uncommon for patients chronically treated with opioids to exhibit opioid induced hyperalgesia (OIH), and this has been widely reported both clinically and experimentally. The molecular substrate for this hyperalgesia is multifaceted, and associated with a complex neural reorganization even in the periphery. For instance, we have recently shown that chronic morphine-induced heat hyperalgesia is associated with an increased expression of GluN2B containing N-methyl-D-aspartate (NMDA) receptors, as well as of the neuronal excitatory amino acid transporter 3/excitatory amino acid carrier 1, in small diameter primary sensory neurons only. Cold allodynia is also a common complaint of patients chronically treated with opioids, yet its molecular mechanisms remain to be understood. Here we present evidence that the cold sensor TRPM8 channel is involved in OIH. After 7 days of morphine administration, we observed an upregulation of TRPM8 channels both by patch clamp recording on sensory neurons and western blot on dorsal root ganglia (DRGs). The selective TRPM8 antagonist RQ-00203078 blocked cold hyperalgesia in morphine treated rats. Also, TRPM8 knockout mice (KO) failed to develop cold hyperalgesia after chronic administration of morphine. Our results demonstrate that chronic morphine upregulates TRPM8 channels, which is in contrast with the previous finding that acute morphine triggers TRPM8 internalization. Perspective Patients receiving chronic opioid are sensitive to cold. We now show in mice and rats that sustained morphine administration induces cold hyperalgesia and an up-regulation of TRPM8. Knockout or selectively blocking TRPM8 reduces morphine induced cold hyperalgesia suggesting TRPM8 is regulated by opioids.

Biochemical Pharmacology

“…Notably, clinical studies on lamotrigine, gabapentin, and amitriptyline specified the inclusion of cold pain patients, and the overall results were positive [147,148]. A rat study also verified that amitriptyline is effective in diabetic animals with associated cold allodynia [149]. However, while venlafaxine and pregabalin were effective for the treatment of diabetic neuropathy, it is unclear if these human trials included patients with cold pain [146,150].…”

Section: Treatment Of Pathological Cold Painmentioning

confidence: 99%

Therapeutic opportunities for targeting cold pain pathways

Yin

Zimmermann

Vetter

et al. 2015

Please cite this article as: Yin K, Zimmermann K, Vetter I, Lewis RJ, Therapeutic opportunities for targeting cold pain pathways, Biochemical Pharmacology (2014), http://dx.doi. org/10.1016/j.bcp.2014.09.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.