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Background: Peripheral nerve stimulation (PNS) has emerged as a promising treatment for refractory neuropathic pain in the upper extremities, particularly for patients unresponsive to conventional therapies. This systematic review and meta-analysis aims specifically to evaluate the effectiveness and safety of nerve stimulation of the brachial plexus (BP) for managing chronic neuropathic pain in the upper extremities.

Methods: A comprehensive literature search was conducted following PRISMA guidelines across major databases, including PubMed, Scopus and Embase. Five studies met the inclusion criteria, encompassing a total of 157 patients with BP or other peripheral nerve injuries. The primary outcome measures included pain reduction and quality of life improvement, assessed through validated pain scales such as the Numerical Rating Scale (NRS) and patient-reported outcomes.

Results: This meta-analysis demonstrated significant reductions in pain scores following BP nerve stimulation (MD: −4.88, 95% CI: −5.80 to −3.96, p < 0.05). Additionally, improvements in quality of life were observed, with over 30% enhancement in Short Form (SF)-36 scores. The overall complication rate was low, with only 9.2% of patients experiencing adverse events, such as lead migration or postoperative infection.

Conclusions: These findings suggest that PNS at the level of the BP is both a safe and effective intervention for the management of refractory neuropathic pain in the upper extremities.

Level of Evidence: Level IV (Therapeutic)

Neuropathic pain in root avulsion brachial plexus injury (BPI) is severe and unrelenting. Routine analgesics and other described methods often provide inadequate pain relief. We report a patient with neuropathic pain following C₈T₁ root avulsion injury, which was successfully managed with end-to-side ulnar sensory branch transfer to the median nerve. Postoperatively, there was a marked reduction in pain score as determined by visual analogue score (VAS) and a marked improvement in the daily sleep interference scale (DSIS). This option may be considered in patients with severe neuropathic pain in lower root avulsion injury in BPI.

Level of Evidence: Level V (Therapeutic)

The Bennett and Xie (1988) model of chronic constriction injury (CCI) investigated the effects of tetramethylpyrazine (TMP) on neuropathic pain-associated behaviors and neuronal apoptosis in the spinal dorsal horn. Fifty-four male rats were randomly divided into sham (group S), CCI (group C) and TMP groups (group T). Each group was divided into subgroups (n = 6 in each group) according the time of sacrifice: 3 d, 7 d and 14 d. Rat sciatic nerves were unligated (group S), or the right sciatic nerve was loosely ligated (groups C and T) to produce CCI. Mechanical withdrawal thresholds (MWTs) and thermal withdrawal latencies (TWLs) were measured, and the rats were sacrificed at different time points post-operation. The L4-L6 sections of the spinal cord were removed. Apoptotic changes were evaluated using the TUNEL method. Immunohistochemistry assessed Bcl-2 and caspase-3 expression. TMP treatment increased MWT and TWL values and Bcl-2 expression, but it reduced neuronal apoptosis and caspase-3 expression in laminae I–II of the spinal dorsal horn. These results suggested that the inhibition of neuronal apoptosis via the modulation of Bcl-2 and caspase-3 proteins in the rat spinal dorsal horn contributed to TMP-induced analgesia.

Electroacupuncture (EA) has been shown to induce potent analgesic effects on neuropathic pain in both patients and rodents. Cell therapy to release antinociceptive agents near the pain processing centers of the spinal cord is a promising next step in the development of treatment modalities. This study investigated the effects of the combination of EA and cell therapy by glial cell line-derived neurotrophic factor (GDNF) on neuropathic pain in rats. The hyperalgesic state was induced by chronic constriction injury (CCI) of the sciatic nerve and fibroblasts genetically modified to secrete bioactive GDNF (FBs-GDNF) were used for cell therapy. Fifty-eight rats with neuropathic pain were randomly divided into five groups (CCI+PBS, n = 11; CCI+FBs-GDNF, n = 12; CCI+EA+PBS, n = 11; CCI+EA+FBs-pLNCX2, n = 12; CCI+EA+FBs-GDNF, n = 12). On the 7th day after CCI, the rats received intrathecal transplantation of FBs-GDNF or control fibroblasts (FBs-pLNCX2). In the meantime, EA was administered once every other day from the 7th day after CCI surgery for 21 days. The paw withdrawal latency (PWL) to radiant heat was measured every other day. The results showed that the ipsilateral PWL of the rats from all three EA treatment groups significantly increased starting on the 12th day compared with the PBS control group. Strikingly, the group which received EA treatment and FBs-GDNF transplantation (CCI+EA+FBs-GDNF) showed a significantly decreased thermal hyperalgesia after 2 weeks post CCI surgery compared with the groups which received EA treatment and FBs-pLNCX2 transplantation (CCI+EA+FBs-pLNCX2) or PBS (CCI+EA+PBS) as well as the FBs-GDNF transplantation group without EA treatment (CCI+FBs-GDNF). Our data suggest that EA and cell therapy can synergistically attenuate hyperalgesia in neuropathic pain rats.

This study was designed to determine the antinociceptive effect and related neuronal mechanism of electroacupuncture (EA) on paclitaxel (PTX)-induced neuropathic pain in mice. PTX (4 mg/kg, i.p.) was administered once a day for 5 consecutive days to induce neuropathic pain. EA stimulation (2 mA, 2 Hz, 30 min) was applied at the ST36 acupoint bilaterally once in every 2 days. Repeated EA stimulation significantly attenuated PTX-induced mechanical allodynia and thermal hyperalgesia. In a separate set of experiment, the antinociceptive effect of a single EA stimulation 8 days after PTX treatment was reduced by intrathecal pretreatment with naloxone (opioid receptor antagonist), idazoxan (alpha2-adrenoceptor antagonist) or propranolol (beta-adrenoceptor antagonist), but not prazosin (alpha1-adrenoceptor antagonist). Moreover, EA remarkably suppressed the PTX-enhanced phosphorylation of the NMDA receptor NR2B subunit in the spinal dorsal horn, and intrathecal pretreatment of naloxone, idazoxan (IDA) or propranolol blocked the effect of EA. In conclusion, EA stimulation at the ST36 acupoint significantly diminished PTX-induced neuropathic pain in mice via the mediation of spinal opioid receptor, alpha2- and beta-adrenoceptors.

Complex regional pain syndrome (CRPS), previously known as reflex sympathetic dystrophy, is attracting more public attention in Japan which is likely a result of the recent upsurge in lawsuits filed against medical institutes. A recent court ruling over a case of injection-needlestick-injury induced CRPS has touched off serious debates among both medical practitioners and legal professionals. Although the court rejected the plaintiff's claims, the high court admitted them in view of the evidence and the entire pleadings and ordered the defendant to pay compensation. As venipuncture is the most frequently conducted and minimally invasive procedure in daily clinical practice, this court decision has attracted tremendous interest throughout the nation, alarming medical practitioners, and encouraging attorneys. The purpose of this article is twofold: to highlight the patient's clinical course in summary based on an unofficial case law report¹ and to provide a scientific perspective on this issue based on recent relevant articles.

The purpose of this study was to identify the clinical characteristics of neuropathic pain in patients with carpal tunnel syndrome. We retrospectively reviewed 143 hands in 127 patients with carpal tunnel syndrome. The neuropathic pain was determined by using the painDETECT as a self-administered psychometric questionnaire to distinguish neuropathic pain. There were no significant differences in the characteristics of the patients with and without neuropathic pain. However, there were significant differences in the pain scores between those with and without neuropathic pain (p < 0.01). Furthermore, there was a significant difference between the existence of night pain in these patients (p < 0.01). Based on the results of the current study, we conclude that it is important to be aware of, and consider the existence of neuropathic pain during the treatment of patients with carpal tunnel syndrome with night pain or a high score on the numerical rating scales of pain.

Background: In Thailand, brachial plexus injury is a common traumatic injury that affects the function of the upper extremity. The current treatments focus mainly on improving the motor and sensory function. Apart from the motor and sensory deficit, these patients usually suffer from pain. Objective: The purpose of this study was to determine the prevalence and factors that relate to neuropathic pain in patients with brachial plexus injury. Methods: We collected data from March 2008 to July 2011. The DN4 Questionnaire was used to diagnose neuropathic pain in 95 patients. Results: The prevalence of neuropathic pain was as high as 76%. Majority of patients presented with hypoesthesia to pin prick, hypoesthesia to touch and numbness. Severity of neuropathic pain was significantly correlated with the type of brachial plexus injury. There was no difference between demographic characteristics of patients. Conclusion: Our study showed that the prevalence of neuropathic pain was high in brachial plexus injured patients. Therefore, surgeons should be aware of this common, yet underestimated, problem in brachial plexus injured patients.

First Asia Pacific Declaration for Chronic Pain Relief to Solve its Major Health Crisis.

ASIA-PACIFIC – Precision medicine for diagnosing and treating neuropathic pain.

ASIA-PACIFIC – Antibiotics overuse causes imbalanced gut microbiome.

ASIA-PACIFIC – Bright lights, big CITI.

REST OF THE WORLD – 2018 Nobel Prize in Physiology or Medicine winners.

REST OF THE WORLD – Women more prone to selected chemotherapy side-effects.

Background: Neurodegenerative diseases, including Alzheimer’s disease, are characterized by progressive neuronal cell loss and nervous system damage. Neuropathic pain, resulting from traumatic injury to sensory nerves, is closely associated with these neurodegenerative conditions. Endoplasmic reticulum (ER) stress, arising from protein misfolding or accumulation of unfolded proteins, plays a crucial role in maintaining cellular homeostasis through the activation of the unfolded protein response (UPR). Interestingly, the ER stress pathway has emerged as a potential link between neuropathic pain and Alzheimer’s disease. To investigate this link, we selected specific drugs with known mechanisms of action: GSK2606414, an EIF-2$\alpha$ phosphorylation inhibitor, Valsartan, which down-regulates ER stress-related proteins, Gemigliptin, known to decrease GRP78 expression, and Melatonin, shown to reduce ATF6 mRNA and protein levels. Additionally, Vemurafenib and Obatoclax were chosen as kinase and Bcl2 inhibitors, respectively. Drug selection was based on data from DrugBank and literature, with their structures obtained from the PubChem database. Main methodologies: Our research aims to identify potential therapeutic targets bridging neuropathic pain and Alzheimer’s disease. Using AutoDock v4.2.6, we conducted molecular docking studies, revealing promising drug–target interactions. We further performed molecular dynamic (MD) simulations for 100 ns using the WEBGRO online server to assess drug-target stability. Additionally, we employed Lipinski screening via the SwissADME web server, assessing pharmacokinetic properties and toxicity. Results: Except for ATF4 (with Metformin), all targets showed favorable affinity toward Obatoclax, with binding energies ranging from −5.32 to −7.48 kcal/mol. The XBP1–Obatoclax complex stability is evaluated using MD simulation. The ADMET screening results indicated that the drugs displayed good intestinal absorption (above 30%), making them suitable for oral administration. Importantly, these drugs showed no inhibitory effects against CYP2D6 isozymes expressed in the CNS. Future perspective: Our in silico findings provide valuable evidence and potential leads for further evaluation and confirmation through in vitro research. The data generated from this study may contribute to the development of novel therapeutics targeting both neuropathic pain and Alzheimer’s disease, offering new hope for patients suffering from these debilitating conditions.