Analgesic effects of nerve growth factor-directed monoclonal antibody on diabetic neuralgia in an animal model.

Current treatment options for diabetic neuralgia are limited and unsatisfactory. Tanezumab, a monoclonal antibody that blocks nerve growth factor (NGF) signaling, has been shown to be effective in relieving the clinical symptoms of osteoarthritis pain, chronic low back pain, cancer pain induced by bone metastasis, and diabetic neuralgia. However, the clinical development of tanezumab has been terminated due to the risk of induction of rapidly progressive osteoarthritis (RPOA), and no other NGF antibodies have been examined for their ability to treat diabetic neuralgia in either animal models or clinical trials. In this study, a humanized high-affinity NGF monoclonal antibody (mAb), huAb45 that could neutralize the interaction between NGF and its high-affinity receptor TrkA. In a mouse diabetic neuralgia model, it effectively relieved neuropathic pain. This study may serve as the necessary foundation for future studies of huAb45 to potentially treat diabetic neuralgia.

Wnt Signaling Pathways: A Role in Pain Processing.

The wingless-related integration site (Wnt) signaling pathway plays an essential role in embryonic development and nervous system regulation. It is critically involved in multiple types of neuropathic pain (NP), such as HIV-related NP, cancer pain, diabetic neuralgia, multiple sclerosis-related NP, endometriosis pain, and other painful diseases. Wnt signaling is also implicated in the pain induced by sciatic nerve compression injury and selective spinal nerve ligation. Thus, the Wnt signaling pathway may be a potential therapeutic target for NP.

Effect of electroacupuncture on expression of p-ERK and p-CREB in the spinal dorsal horn of diabetic neuropathic pain rats / 中华物理医学与康复杂志

Objective:To observe any effect of electroacupuncture (EA) on the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) in the spinal dorsal horns of diabetics experiencing neuropathic pain.Methods:Eight rats were randomly selected from 30 healthy male Sprague-Dawley rats as the normal group (N), and the remaining twenty-two rats were treated with a single high-dose intraperitoneal injection of streptozotocin (STZ) to establish a neuropathic pain model. The rats modeled successfully were randomly divided into a model group (M, n=8) and an EA group ( n=8). In the EA group, electroacupuncture was applied at the bilateral Hou san li and Kunlun acupoints starting on the 15th day after the STZ injection. The daily sessions lasted 30 minutes for 1 week. Body weight (BW), fasting blood glucose (FBG) and paw withdrawal latency (PWL) were observed before the STZ injection and on the 7th, 14th, and 21st days afterward. The expression of p-ERK1/2 and p-CREB in the dorsal horns of the rats′ spinal cords was detected using western blotting. The count of p-CREB-positive cells in the dorsal horns and their co-localization with neurons was detected using immunofluorescence. Results:In comparison with the N group, the average BW of the M group on the 7th, 14th and 21st days after the STZ injection was significantly lower, while the average FBG was significantly higher. There was no significant difference between the M and N groups in the average PWL on the 7th day after the STZ injection, but it had decreased significantly in the M group on the 14th and 21st days. Compared with the M group, the average PWL of the EA group was significantly longer on the 21st day after the injection. The expression of p-ERK1/2 and p-CREB protein in the spines of the M group was significantly higher than in the N group. p-CREB positive cells were more numerous in the M group compared with the N group, while in the EA group they were fewer. P-CREB was co-located with neurons in the spinal dorsal horn.Conclusion:EA can alleviate neuropathic pain effectively, perhaps by inhibiting the expression of p-ERK1/2 and p-CREB in the dorsal horns of the spinal cord.

Oral pharmacotherapeutics for the management of peripheral neuropathic pain conditions - a review of clinical trials.

INTRODUCTION: Epidemiological studies have shown that 6.9-10% of people suffer from neuropathic pain, a complex painful condition which is often undertreated. Data regarding the effectiveness of treatment options for patients with neuropathic pain is inconsistent, and there is no single treatment option that shows cost-effectiveness across studies. AREAS COVERED: In this narrative review, the authors present the results of different prospective, randomized controlled trials, systematic reviews and meta-analyses assessing the effects of different oral medications in the management of various peripheral neuropathic pain conditions. The authors discuss the effectiveness of commonly used oral medications such as voltage-gated calcium channels antagonists, voltage-gated sodium channel antagonists, serotonin-norepinephrine reuptake inhibitors, NMDA antagonists, and medications with other mechanisms of action. EXPERT OPINION: Most of the presented medications were more effective than placebo; however, when compared to each other, none of them were significantly superior. The heterogeneity of the studies looking into different oral neuropathic conditions has been the major issue that prevents us from making stronger recommendations. There are multiple reasons including high placebo responsiveness, improperly treated underlying comorbidities (particularly anxiety and depression), and inter-patient variability. Different sensory phenotypes should also be taken into consideration when designing future clinical trials for neuropathic pain.

Effects of extracorporeal shock waves on neuralgia in diabetic rats.

OBJECTIVE: The aim of this study was to observe the effects of extracorporeal shock waves (ECSWs) on neuralgia in diabetic rats. MATERIALS AND METHODS: Diabetic neuralgia model was established in rats via injection of streptozotocin. The rats were divided into diabetic neuralgia group (Group A, n=6) and ECSW treatment group (Group B, n=6). Another six rats were taken as control group (Group C, n=6). The mechanical withdrawal threshold (MWT) and thermal withdrawal latencies (TWLs) were measured at specific points throughout the experiment, and the sciatic nerve was bluntly severed under anesthesia after the last measurement. The protein expressions of Sphk1 and TNF-α were detected by Western blot, and the mRNA expressions of Sphk1 and TNF-α were detected by reverse transcription PCR. The structure of the sciatic nerve was observed by electron microscopy. RESULTS: Compared with Group C, MWT and TWLs were decreased significantly in Groups A and B (P< 0.05). The protein expressions of TNF-α and Sphk1 in Groups A and B were both significantly higher than those in Group C (P<0.05), with higher expression in Group A than in Group B (P<0.05). The mRNA expressions of TNF-α and Sphk1 were similar. Electron microscopy showed the intact structure of the myelin sheaths of the sciatic nerve fibers in Group C, whereas the structure of the nerve fibers was damaged, with a large number of vacuoles in the myelin sheath in Group A. In Group B, the vacuoles were occasionally formed on the sciatic nerve myelin sheath, with more compact and tidy layer arrangement compared with Group A. CONCLUSION: ECSWs can relieve neuralgia in diabetic rats. Sphk1 and TNF-α may be involved in the occurrence and development of diabetic peripheral neuralgia.