Short-Term Supraorbital Nerve Stimulation and Pain Relief for Acute and Subacute Ophthalmic Herpetic Neuralgia: A Randomized Controlled Crossover Trial.

BACKGROUND: Herpes zoster ophthalmicus (HZO) is a kind of refractory disease, and treating it is important for preventing postherpetic neuralgia (PHN). But the evidence surrounding the current treatment options for these conditions is controversial, so exploring reasonable clinical treatment strategies for HZO is necessary. Neuromodulation is an excellent modality for the treatment of various neuropathic pain conditions. This trial was designed to evaluate the effectiveness of short-term supraorbital nerve stimulation (SNS) and the supraorbital nerve block (SNB) for HZO. OBJECTIVES: To determine whether short-term SNS relieves acute and subacute ophthalmic herpetic neuralgia. STUDY DESIGN: This prospective randomized controlled crossover trial compared short-term SNS to SNB. SETTING: The operating room of a pain clinic. METHODS: Patients with acute or subacute ophthalmic herpetic neuralgia were recruited. The patients were randomly assigned to receive either SNS or SNB. The primary outcome being measured was each patient's Visual Analog Scale (VAS) score at 4 weeks. The secondary outcomes under measurement were the proportion of patients who achieved ≥ 50% pain relief, sleep quality, medicine consumption, and adverse events. Crossover after 4 weeks was permitted, and patients were followed up to 12 weeks. RESULTS: Overall, 50 patients were included (n = 25/group). At 4 weeks, the patients who received SNS achieved greater pain relief, as indicated by their significantly different VAS scores from those of the SNB group (mean difference: -1.4 [95% CI, -2.29 to -0.51], P < 0.05). Both groups showed a significant decrease in pain level from the baseline (all P < 0.05). Overall, 72% and 44% of the SNS and SNB patients experienced ≥ 50% pain relief, respectively (OR: 0.31 [95% CI, 0.09 to 0.99], P < 0.05), and 68% and 32% of SNS and SNB patients, respectively, had VAS scores < 3 (OR: 0.22 [95% CI, 0.07 to 0.73], P < 0.05). Compared to the SNB group, the SNS group had better sleep quality, lower ophthalmic neuralgia, a lower proportion of further treatment, and lower analgesic intake. Overall, 18 patients received SNS alone, and 16 patients crossed over from SNB to SNS. The VAS scores, sleep quality, ophthalmic neuralgia, and trend of medicine intake were not significantly different between the groups (all P > 0.05). No serious complications occurred. LIMITATIONS: This study was nonblind. CONCLUSIONS: Short-term SNS is effective for controlling acute or subacute ophthalmic herpetic neuralgia. Combining SNS with SNB yields no additional benefits.

Spinal Cord Stimulation Alleviates Neuropathic Pain by Attenuating Microglial Activation via Reducing Colony-Stimulating Factor 1 Levels in the Spinal Cord in a Rat Model of Chronic Constriction Injury.

BACKGROUND: Spinal cord stimulation (SCS) is an emerging, minimally invasive procedure used to treat patients with intractable chronic pain conditions. Although several signaling pathways have been proposed to account for SCS-mediated pain relief, the precise mechanisms remain poorly understood. Recent evidence reveals that injured sensory neuron-derived colony-stimulating factor 1 (CSF1) induces microglial activation in the spinal cord, contributing to the development of neuropathic pain (NP). Here, we tested the hypothesis that SCS relieves pain in a rat model of chronic constriction injury (CCI) by attenuating microglial activation via blocking CSF1 to the spinal cord. METHODS: Sprague-Dawley rats underwent sciatic nerve ligation to induce CCI and were implanted with an epidural SCS lead. SCS was delivered 6 hours per day for 5 days. Some rats received a once-daily intrathecal injection of CSF1 for 3 days during SCS. RESULTS: Compared with naive rats, CCI rats had a marked decrease in the mechanical withdrawal threshold of the paw, along with increased microglial activation and augmented CSF1 levels in the spinal dorsal horn and dorsal root ganglion, as measured by immunofluorescence or Western blotting. SCS significantly increased the mechanical withdrawal threshold and attenuated microglial activation in the spinal dorsal horn in CCI rats, which were associated with reductions in CSF1 levels in the spinal dorsal horn and dorsal roots but not dorsal root ganglion. Moreover, intrathecal injection of CSF1 completely abolished SCS-induced changes in the mechanical withdrawal threshold and activation of microglia in the spinal dorsal horn in CCI rats. CONCLUSIONS: SCS reduces microglial activation in the spinal cord and alleviates chronic NP, at least in part by inhibiting the release of CSF1 from the dorsal root ganglion ipsilateral to nerve injury.

Comparison of Two Different Pulsed Radiofrequency Modes for Prevention of Postherpetic Neuralgia in Elderly Patients With Acute/Subacute Trigeminal Herpes Zoster.

OBJECTIVE: Trigeminal postherpetic neuralgia (PHN) is often refractory to treatment. Pulsed radiofrequency (PRF) neuromodulation can help in preventing PHN after herpes zoster. This study aimed to compare the efficacy and safety of two different PRF modes on gasserian ganglion neuromodulation in elderly patients with acute/subacute trigeminal herpes zoster. MATERIALS AND METHODS: A total of 120 elderly patients with acute or subacute (within past three months) trigeminal herpes zoster were randomized to receive either a single cycle of high-voltage, long-duration PRF (HL-PRF group; N = 60) or three cycles of standard PRF (S-PRF group; N = 60). Patients were followed up for six months after treatment. Visual analog scale (VAS) pain score, 36-Item Short Form Health Survey (SF-36) score, and pregabalin at baseline and at different time points during follow-up were recorded. RESULTS: VAS and SF-36 scores declined significantly from baseline levels in both groups (p < 0.001). The scores were significantly lower in the HL-PRF group than in the S-PRF group at some time points (p < 0.05). The mean dose of pregabalin was significantly lower in the HL-PRF group than in the S-PRF group on days 3, 14, and 28 after treatment (p < 0.05). No serious adverse events occurred in either group. CONCLUSION: HL-PRF neuromodulation of the gasserian ganglion appears to be more effective than S-PRF for preventing PHN in the elderly. CLINICAL TRIAL REGISTRATION: ChiCTR2000038775.

Astaxanthin alleviates inflammatory pain by regulating the p38 mitogen-activated protein kinase and nuclear factor-erythroid factor 2-related factor/heme oxygenase-1 pathways in mice.

Inflammatory pain is a complex process that has a substantial negative impact on post-injury quality of life. Astaxanthin (AST), which is a lipid-soluble red-orange carotenoid that is found in lobsters, inhibits the development and maintenance of inflammation in mice via its antioxidant and anti-inflammatory activities. However, the specific mechanisms underlying these effects remain unclear. In this study, we aimed to elucidate the mechanism by which astaxanthin alleviated inflammation using a mouse model with Complete Freund's adjuvant (CFA)-induced inflammatory pain. Mechanical allodynia and thermal hyperalgesia were observed on days 1-14 post CFA injection. Expression of p38 mitogen-activated protein kinase (MAPK) in the left paw and L4-6 dorsal root ganglia (DRG) were upregulated in the CFA-induced mice. Expression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were also increased. Astaxanthin relieved mechanical allodynia and thermal hyperalgesia induced by CFA and inhibited the inflammatory response (e.g., infiltration of inflammatory cells and production of inflammatory factors) in the ipsilateral paw and DRG. Additionally, AST  inhibited p38 MAPK and enhanced Nrf2/HO-1 contents in the left paw and DRG, and reversed the pain induced by p38 MAPK agonist and Nrf2 inhibitors. These findings suggest that AST exerts anti-inflammatory effects and regulates p38 MAPK and Nrf2/HO-1 to alleviate inflammatory pain. AST may be a potential therapeutic agent for relieving inflammation.

Neurolytic Splanchnic Nerve Block and Pain Relief, Survival, and Quality of Life in Unresectable Pancreatic Cancer: A Randomized Controlled Trial.

BACKGROUND: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors' primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected. METHODS: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death. RESULTS: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed. CONCLUSIONS: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer.

Efficacy of Pulsed Radiofrequency or Short-Term Spinal Cord Stimulation for Acute/Subacute Zoster-Related Pain: A Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the final stage of varicella zoster infection and a severe refractory neuropathic pain. Hence preventing transition of herpes zoster-related pain to PHN is a very important therapeutic principle for patients at an early stage, especially for older patients.Both pulsed radiofrequency (PRF) and short-term spinal cord stimulation (stSCS) have been proven to be effective to relieve acute/subacute zoster-related pain. However, which treatment could achieve better analgesic effects remains unclear. OBJECTIVES: This study aimed to investigate the therapeutic efficacy and safety of PRF and stSCS in patients with acute/subacute zoster-related pain. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Department of Pain Medicine, the First Affiliated Hospital of China Medical University. METHODS: Ninety-six patients with acute/subacute zoster-related pain were equally randomized into 2 groups: PRF group and stSCS group. Patients in the different groups were treated with high-voltage, long-duration PRF or stSCS. The therapeutic effects were evaluated using a Numeric Rating Scale (NRS-11) and the 36-Item Short Form Health Survey (SF-36) at different time points. The average dose of pregabalin (mg/d) administrated at different time points was also recorded. RESULTS: The posttreatment NRS-11 scores in the 2 groups were significantly lower compared with baseline (P < 0.001). The NRS-11 scores in the stSCS group were significantly lower than those in the PRF group at 30 and 180 days after treatments (P < 0.05). The SF-36 scores of general health, social function, role-emotional, mental health, bodily pain, physical function, physical role, and vitality could be significantly improved at each time point after treatments in the 2 groups. Some SF-36 scores could be significantly improved at some time points in the stSCS group compared with the PRF group. The rescue drug (pregabalin) dosages were lower in the stSCS group than those in the PRF group at days 90 and 180 after treatments. There was no bleeding at the puncture site, infection, postoperative paresthesia, nerve injury, or any other serious adverse effects in either group. LIMITATIONS: Single-center study, relatively small number of patients. CONCLUSIONS: PRF and stSCS are both effective and safe therapeutic alternatives for patients with acute/subacute zoster-related pain, however, stSCS could achieve more pain relief and improvement of life quality compared with PRF.

Short-Term Peripheral Nerve Stimulation Relieve Pain for Elder Herpes Zoster Ophthalmicus Patients: A Retrospective Study.

OBJECTIVE: Ophthalmic postherpetic neuralgia (PHN) is the final stage of herpes zoster (HZ) ophthalmicus and a severe refractory neuropathic pain, thus there is no curative treatment that could alleviate pain and reduce the incidence of ophthalmic PHN now. The purpose of this study is to evaluate therapeutic efficacy of short-term peripheral nerve stimulation (PNS) for elder patients with HZ ophthalmicus. MATERIALS AND METHODS: We performed a retrospective study from March 2015 to August 2019 in our pain department. All the HZ ophthalmicus patients underwent supraorbital nerve short-term PNS were included. The patients' data, including numeric rating scale (NRS), 36-Item short form health survey (SF-36), and analgesic consumptions, were retrospectively analyzed. Severe side effects also were recorded. RESULTS: A total of 68 patients were enrolled in this study. The NRS scores were significantly decreased at different time points after short-term PNS compared to baseline (p < 0.001). The SF-36 scores, including general health, social function, emotional role, mental health, bodily pain, physical functioning, physical role, and vitality, were significantly improved at different time points after treatment (p < 0.001). The average dosages of tramadol and pregabalin administered (mg/d) were both significantly reduced compared to baseline (p < 0.001). There was no bleeding, infection, pain increase, and other side effects after treatment. CONCLUSIONS: Short-term PNS is an effective and safe therapeutic alternative for elder patients with HZ ophthalmicus and could reduce the incidence of ophthalmic PHN.

Patient-controlled subcutaneous analgesia using sufentainil or morphine in home care treatment in patients with stage III-IV cancer: A multi-center randomized controlled clinical trial.

PURPOSE: Patient-controlled subcutaneous analgesia (PCSA) with sufentanil is an alternative analgesia strategy in patients with stage III-IV cancer; however, its efficacy and safety have not been fully investigated. METHODS: From May 10, 2017 to November 10, 2017, 120 patients with stage III-IV cancer suffering from moderate to severe pain were prospectively enrolled from six hospitals and randomized to receive PCSA with morphine (control group) or sufentanil (intervention group). Before the PCSA and on days 1, 3, 7, 14, 28, and 56 after treatment, the numeric rating scale (NRS) and 36-item Short Form health survey (SF-36) were completed for each patient and the side effects were also recorded. RESULTS: No significant differences (P > .05) were observed in the preoperative NRS score and the SF-36 parameters between the two groups. Patients in the intervention group achieved better pain relief, as indicated by lower NRS scores at days 14 (P = .040), 28 (P < .001), and 56 (P < .001) after PCSA device implantation (vs control group). Furthermore, the patients in the intervention group also achieved a better life quality, as indicated by the physical role, general health, social function body pain, and mental health scores. Finally, the patients receiving sufentanil showed lower levels of nausea and somnolence than those in the control group. CONCLUSION: PCSA with sufentanil achieves better pain control and life quality as well as fewer adverse reactions in stage III-IV cancer patients with pain and may be a promising pain management in these patients. TRIAL REGISTRATION: This study was registered at chictr.org.cn with the trial number: ChiCTR-IPR-17011280.

High-Voltage, Long-Duration Pulsed Radiofrequency on Gasserian Ganglion Improves Acute/Subacute Zoster-Related Trigeminal Neuralgia: A Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Trigeminal postherpetic neuralgia is a severe neuropathic pain and often refractory to existing treatment, it develops secondary to herpes zoster-infected Gasserian ganglion. Therefore, it is important to prevent the transition of acute/subacute zoster-related pain to trigeminal postherpetic neuralgia. Despite numerous studies, the optimal intervention that reduces trigeminal postherpetic neuralgia incidence is still unknown. OBJECTIVES: This study aimed to evaluate the efficacy and safety of high-voltage, long-duration pulsed radiofrequency (PRF) on the Gasserian ganglion in patients with acute/subacute zoster-related trigeminal neuralgia. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Department of Pain Medicine, the First Affiliated Hospital of China Medical University. METHODS: Ninety-six patients with acute/subacute zoster-related trigeminal neuralgia were equally randomly assigned into 2 groups. The electrode needle punctured the Gasserian ganglion guided by computed tomography in every patient. High-voltage, long-duration PRF at 42°C for 900 seconds was applied in the PRF group (n = 48). It was also applied in the sham group (n = 48) without radiofrequency energy output. The therapeutic effects were evaluated using a visual analog scale (VAS) and the 36-Item Short Form Health Survey (SF-36) at different time points. The average dosage of pregabalin (mg/d) administrated within the first month after treatment was also recorded. RESULTS: The postprocedure VAS scores in the PRF group were significantly lower than those in the sham group at different time points after treatment (P < 0.01). The SF-36 scores, which included physical functioning, physical role, bodily pain, general health perceptions, vitality, social function, emotional role, and the mental health index, were significantly improved at the sixth month after treatment in the PRF group compared with the sham group (P < 0.01). The average dosage of pregabalin administered (mg/d) within the first month after treatment was also significantly reduced in the PRF group compared with the sham group (P < 0.01). There were no bleeding, infection, or other severe side effects in both groups. LIMITATIONS: Single center study, relatively small number of patients. CONCLUSIONS: High-voltage, long-duration PRF on the Gasserian ganglion is an effective and safe therapeutic alternative for patients with acute/subacute zoster-related trigeminal neuralgia. KEY WORDS: Pulsed radiofrequency, zoster-related trigeminal neuralgia, visual analog scale, 36-Item Short Form Health Survey.

Prospective Evaluation of Nasopharyngeal Intubation During Radiofrequency Thermocoagulation of the Trigeminal Ganglion.

AIMS: To investigate whether nasopharyngeal airway (NPA) intubation could reduce the risk of complications caused by radiofrequency thermocoagulation (RFT) of the trigeminal ganglion. METHODS: From November 1, 2014 to May 1, 2015, 200 patients treated with sedation (combination of sufentanil and propofol) were randomly divided into two groups, one in which NPA intubation was used (intervention group) and one in which it was not used (control group). The primary outcome was the frequency of hypoxemia, and secondary outcomes were the frequency of hypotension, nasal mucosa damage, corneal numbness, masticatory weakness, palsies of other cranial nerves, and intracranial hemorrhage. Statistical analyses were performed by using the Statistical Package for Social Sciences version 19.0. A P value < .05 was considered to reflect statistical significance. Differences in the frequencies of adverse events between the two groups were assessed by using Fisher exact test. RESULTS: Five patients in the intervention group showed minor nasal mucosa injury (P = .027). Hypoxemia (19 vs 3, P < .001), corneal numbness (12 vs 4), and masticatory weakness (11 vs 3) occurred more frequently in the control group than in the intervention group (P < .05). No significant differences in the incidence of hypotension or palsies of other cranial nerves were observed between the two groups (P > .05). CONCLUSION: NPA intubation can reduce the frequency of hypoxemia and complications related to the thermocoagulation of the trigeminal ganglion with minor risks for nasopharyngeal injury.

Edaravone improves spatial memory and modulates endoplasmic reticulum stress-mediated apoptosis after abdominal surgery in mice.

Patients who receive major surgery often develop postoperative cognitive dysfunction (POCD); however, there is a lack of effective management as the pathogenesis of this disorder has not been fully elucidated. The neuroprotective effects of edaravone have been characterized in both in vitro cultured cells and in experimental animal models. The present study aimed to determine the potential role of edaravone in surgery-induced cognitive decline in mice. Animals were assigned to three groups: Control group (n=32), where mice received local anesthesia; surgery group (n=32), where mice underwent abdominal surgery under anesthesia; and edaravone group (n=32), where mice received abdominal surgery and were administered with edaravone (3 mg/kg). Morris water maze and T-maze tests demonstrated that edaravone attenuated surgery-induced cognitive impairment. Nissl staining indicated that edaravone prevented neuronal loss in the hippocampus of mice that underwent surgery. Furthermore, treatment with edaravone mitigated the surgery-induced upregulation of glucose-regulated protein 78 and CCAAT-enhancer-binding homologous protein and reduced the number of terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling-positive nuclei in mice hippocampi. In conclusion, edaravone may prevent POCD-induced neuronal apoptosis through attenuating endoplasmic reticulum stress.

Efficacy of Short-Term Spinal Cord Stimulation in Acute/Subacute Zoster-Related Pain: A Retrospective Study.

BACKGROUND: Postherpetic neuralgia (PHN) is a refractory condition that impairs the patient's quality of life (QoL), it develops secondary to herpes zoster infection. Therefore, it's important to prevent the transition of acute/subacute zoster-related pain to PHN. Despite of numerous studies, the optimal intervention that reduces PHN incidence is still unknown. OBJECTIVE: We evaluate the efficacy of short-term spinal cord stimulation (stSCS) in patients with refractory acute/subacute zoster-related pain. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center/teaching hospital. METHODS: A total of 46 patients who presented with acute/subacute zoster-related pain, and had previously failed conventional therapies, underwent stSCS treatment. Visual analog scale (VAS), Short Form Health Survey 12 items (SF-12), and analgesic consumptions were recorded before stSCS, post-stSCS, 2 weeks, and 1, 3, 6, 9, and 12 months after stimulation. RESULTS: The VAS scores at post-stSCS, 2 weeks, and 1, 3, 6, 9, and 12 months after stSCS treatment were significantly decreased compared with the baseline score (P < 0.001). Thirty-two patients (69.6%, 32/46) achieved the minimal clinically important difference (MCID), including 18 patients (39.1%, 18/46) who achieved complete pain relief (VASless than orequal to2). During the follow-up period, the efficacy of stSCS didn't decrease and VAS scores were declining. Similarly, SF-12 scores and analgesic consumptions improved after stSCS treatment. The efficacy of stSCS did not differ significantly among patients with different durations of acute/subacute zoster-related pain starting from the onset of rash. No serious adverse effects were observed in the entire follow-up period. LIMITATIONS: This study was not a randomized prospective controlled study. We did not compare the outcomes with patients presenting with mild or moderate pain, and did not compare the efficacy of stSCS treatment with conventional therapies. CONCLUSIONS: stSCS is a safe, effective, and less invasive analgesic method for patients with refractory acute/subacute zoster-related pain. KEY WORDS: Herpes zoster, zoster-related pain, postherpetic neuralgia, spinal cord stimulation, VAS.

Bipolar High-Voltage, Long-Duration Pulsed Radiofrequency Improves Pain Relief in Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is often refractory to existing treatments. Treatment of the dorsal root ganglion (DRG) using monopolar pulsed radiofrequency (PRF), which is a non- or minimally neurodestructive technique, is not efficacious in all patients. OBJECTIVES: This study aimed to determine the safety and clinical efficacy of bipolar high-voltage, long-duration PRF on the DRG in PHN patients. STUDY DESIGN: Self before-after controlled clinical trial. SETTING: Department of Pain Medicine, the First Affiliated Hospital of China Medical University. METHODS: Ninety patients diagnosed with PHN for > 3months were included. Bipolar high-voltage, long-duration PRF at 42°C for 900 seconds was applied after the induction of paresthesias covered the regions of hyperalgesic skin. The therapeutic effects were evaluated using a visual analog scale (VAS) and the 36-item Short Form health survey (SF-36) before treatment and one, 4, 8, and 12 weeks after PRF. RESULTS: The VAS scores at one, 4, 8, and 12 weeks after PRF treatment were significantly lower than before treatment (P < 0.001). The SF-36 scores, which included physical functioning, physical role, bodily pain, general health perceptions, vitality, social function, emotional role, and the mental health index, were significantly improved up to 12 weeks after PRF treatment (P < 0.001). No serious adverse effects were identified following treatment. The main adverse reactions included pain, tachycardia, and high blood pressure (especially when the field strength was enhanced). LIMITATIONS: Single center study, relatively small number of patients, lack of a control group. CONCLUSION: Bipolar high-voltage, long-duration PRF on the DRG is an effective and safe therapeutic alternative for PHN patients. This treatment could improve the quality of life of PHN patients. CLINICAL TRIAL REGISTRATION: NO ChiCTR-OCS-14005461.

Houttuynia cordata Thunb reverses oxaliplatin-induced neuropathic pain in rat by regulating Th17/Treg balance.

Oxaliplatin is a widely used anti-advanced colorectal cancer drug, while it could induce neuropathy. Houttuynia cordata Thunb (HCT) has a wide range of biological activities, such as anti-inflammation, anti-cancer, and immune regulation. In the present study, we investigated the effect of HCT on oxaliplatin-induced neuropathy in rat models. HCT (1000 mg/kg/day) significantly decreased the number of withdrawal responses and the withdrawal latency in oxaliplatin-treated rats. HCT could down-regulated the serum levels of Interleukin-6 (IL-6) and macrophage inflammatory protein1-α (MIP-1α) in oxaliplatin-treated rats. Th17/Treg balance was reversed by HCT in oxaliplatin-treated rats by regulating PI3K/Akt/mTOR signaling pathway. The present results suggest that HCT is useful as a therapeutic drug for oxaliplatin-induced neuropathic pain.

Interleukin17A Promotes Postoperative Cognitive Dysfunction by Triggering ß-Amyloid Accumulation via the Transforming Growth Factor-ß (TGFß)/Smad Signaling Pathway.

Although postoperative cognitive dysfunction (POCD) is relatively common in elderly patients who have undergone major surgery, the mechanisms underlying this postoperative complication are unclear. Previously, we have investigated the role of cytokine-mediated hippocampal inflammation in the development of POCD in a rat model. Here, we sought to determine in mice the role of cytokine interleukin17A (IL17A) in POCD and to characterize the associated signaling pathways. Old mice underwent hepatectomy surgery in the presence or absence of IL17A monoclonal antibody, and cognitive function, hippocampal neuroinflammation, and pathologic markers of Alzheimer's disease (AD) were assessed. We found that the level of IL17A in the hippocampus was increased in hepatectomy mice and that cognitive impairment after surgery was associated with the appearance of certain pathological hallmarks of AD: activation of astrocytes, ß-amyloid1-42 (Aß1-42) production, upregulation of transforming growth factor-ß (TGFß), and increased phosphorylation of signaling mother against decapentaplegic peptide 3 (Smad3) protein in the hippocampus. Surgery-induced changes in cognitive dysfunction and changes in Aß1-42 and TGFß/Smad signaling were prevented by the administration of IL17A monoclonal antibody. In addition, IL17A-stimulated TGFß/Smad activation and Aß1-42 expression were reversed by IL17A receptor small interfering RNA and a TGFß receptor inhibitor in cultured astrocytes. Our findings suggest that surgery can provoke IL17A-related hippocampal damage, as characterized by activation of astrocytes and TGFß/Smad pathway dependent Aß1-42 accumulation in old subjects. These changes likely contribute to the cognitive decline seen in POCD.