Gender differences in the antinociceptive effect of tramadol,alone or in combination with gabapentin,in mice

Gender difference in the antinociceptive effect of tramadol and gabapentin (alone or in combination) were investigated in mice. For investigation of acute antinociceptive effect, tramadol and gabapentin were administered to mice by intraperitoneal injection and per os, respectively, and antinociceptive activity was measured by the tail-flick test 30 min after drug administration. For investigation of the development of antinociceptive tolerance to analgesics, mice were injected with tramadol (60 mg/kg), alone or in combination with gabapentin (75 mg/kg), twice daily for seven consecutive days and the tail-flicks were tested on experimental days 1, 3, 5 and 7. Results showed there was a lower ED₅₀ value of tramadol antinociception in males than in females, indicating that females were less sensitive to the drug. Gabapentin produces a limited antinociception in both males and females. The combination of gabapentin and tramadol produced synergistic effect without gender difference. Repeated administration of tramadol produced antinociceptive tolerance in both genders. Gabapentin produced synergistic effect in tramadol-tolerant mice and repeated administration of gabapentin did not alter the synergistic effect in tramadol-tolerant mice. Because females show a higher overall prevalence of pain and less sensitivity to opioids, our finding may suggest a clinical significance of combined use of the two drugs.     

Triamcinolone-Procaine in the Treatment of Zoster and Postzoster Neuralgia

Twenty-four patients with herpes zoster were treated with injections of 2 percent procaine hydrochloride containing 2 mg of triamcinolone per ml. The treatments were given subcutaneously under the cutaneous lesions and in areas of pain. The results were excellent in 22 patients. There was one failure—postzoster neuralgia in an 82-year-old woman.Of 12 patients with postherpetic neuralgia, eight had improvement of 70 to 90 percent and three had complete relief.There were no significant complications in either group.     

普瑞巴林、加巴喷丁联合神经阻滞治疗带状疱疹后神经痛的临床疗效比较

目的:比较普瑞巴林、加巴喷丁联合神经阻滞治疗带状疱疹后神经痛(PHN)的临床疗效。方法:选择2014年8月至2016年11月我院门诊收治的带状疱疹后神经痛患者80例,并将其随机分为两组,每组40例。A组患者接受普瑞巴林联合神经阻滞治疗,B组患者接受加巴喷丁联合神经阻滞治疗,比较两组患者治疗前后的视觉疼痛模拟(VAS)评分、失眠严重程度指数(ISI)评分、生活质量满意指数(LSIB)评分及治疗期间不良反应的发生情况。结果:A组患者治疗后4、7、14 d的VAS评分均显著低于B组(P0.05),LSIB评分显著高于B组(P0.05),A组患者治疗后4、7 d的ISI评分均显著低于B组(P0.05);A组发生不良反应的总发生率显著低于B组(P0.05)。结论:普瑞巴林联合神经阻滞治疗PHN缓解疼痛和失眠的效果显著优于巴喷丁联合神经阻滞治疗,其可显著提高患者的生活质量,并减少不良反应。     

加巴喷丁联合射频脉冲、神经阻滞治疗带状疱疹后神经痛的效果

摘要 目的：探讨加巴喷丁联合脉冲射频、神经阻滞治疗带状疱疹后遗神经痛的效果。方法：本研究选取106例确诊为带状疱疹后遗神经痛的患者,采用随机数表法将其分为对照组A（36例）、试验组B（35例）和试验组C（35例）。A组患者采用口服加巴喷丁进行治疗,B组患者采用加巴喷丁联合神经阻滞治疗,C组患者采用加巴喷丁联合脉冲射频治疗,观察比较三组患者的治疗效果,分别对视觉模拟评分（VAS）、夜间睡眠评分（SRSS）、疼痛程度（NRS）、不良反应及综合疗效进行统计评估。结果：治疗3天、7天、14天和1月后,与对照组A比较,B、C组患者的VAS、SRSS和NRS评分较治疗前均有显著降低（P<0.05）;试验组B、C不良反应发生率分别为8.57%（3/35）和5.71%（2/35）,对照组A不良反应发生率为22.22%（8/36）,试验组不良反应发生率显著低于对照组,差异具有统计学意义（P<0.05）。结论：相较于使用加巴喷丁和加巴喷丁联合神经阻滞这两种治疗方案,加巴喷丁联合射频脉冲及神经阻滞治疗带状疱疹后遗神经痛能够在短期内有效缓解患者疼痛并改善睡眠状况。     

HSV gene transfer in the treatment of chronic pain

It has proven difficult to use systemic administration of small molecules to selectively modulate nociception. Over the past decade, we and others have developed non-replicating herpes simplex virus (HSV)-based vectors to treat chronic pain. Subcutaneous inoculation of an HSV vector effectively transduces sensory neurons in the dorsal root ganglion; release of transgene-coded inhibitory neurotransmitters or anti-inflammatory peptides reduces pain-related behaviors in rodent models of chronic inflammatory and neuro-pathic pain. A phase 1 trial of this therapy in patients is set to begin soon.     

Antinociceptive effect of amitriptyline in mice of acute pain models

Tricyclic antidepressant drugs induce antinociceptive effect and suggest that their analgesic action could be related to the monoaminergic activity of the drugs. The analgesic activity of amitriptyline was observed in mouse models of acute pain. Mice were divided into different groups and were given amitriptyline in different doses alone and in combination with morphine. Reaction time in Hot-Plate and Tail-Flick tests was observed. Results showed that amitriptyline had antinociceptive effect in acute pain state in experimental models. Amitriptyline in combination with morphine had better analgesic effect than the morphine alone in Hot-Plate test.     

A comparison of the glutamate release inhibition and anti-allodynic effects of gabapentin, lamotrigine, and riluzole in a model of neuropathic pain

The effects of treatment with the anti-convulsant agents, lamotrigine and riluzole were compared with gabapentin in a rat experimental model of neuropathic pain. Rats were treated intraperitoneally, with gabapentin (30, 100 and 300 mg/kg), lamotrigine (2, 10 and 50 mg/kg) or riluzole (6 and 12 mg/kg) prior to, and every 12 h for 4 days following chronic constriction injury (CCI) of the sciatic nerve. Mechanical and cold sensitivity were assessed prior to surgery (baseline) and then at 4, 8 and 12 days following CCI. The four-day treatment with each of the agents was effective at producing reductions in the development of mechanical and cold hypersensitivity for periods ranging from the fourth to 12th day. The highest doses of each of the agents were also assessed on formalin-induced nociceptive behaviors and on formalin-induced increases in extracellular glutamate (Glu) and aspartate (Asp) in the spinal cord dorsal horn (SCDH) of awake behaving rats using in vivo microdialysis. Nociceptive scores in formalin test were significantly decreased by gabapentin (300 mg/kg i.p.) and riluzole (12 mg/kg i.p.), but not by lamotrigine (50 mg/kg i.p.). Formalin-induced increases in glutamate levels in SCDH were lowered significantly, as compared with the controls, with all drugs both in the first phase and second phases, with the greatest effects for riluzole and gabapentin. Similar suppressive effects of the drugs were observed on formalin-induced increases in spinal aspartate, except that gabapentin and lamotrigine produced effects only during the second phase. Riluzole produced profound and prolonged reductions in the spinal levels of glutamate and aspartate both for basal and formalin-stimulated release. In conclusion, the results suggest that the anti-convulsant agents gabapentin, lamotrigine and riluzole may reduce the development of hyperalgesia in a rat model of neuropathic pain by reducing the spinal release of glutamate. Riluzole's pronounced suppressive effects on spinal EAA levels is attributed to its established role as a glutamate release inhibitor and an enhancer of glutamate transporter activity.     

原发性三叉神经痛和疱疹后三叉神经痛临床特征及射频热凝术后效果分析

摘要 目的：探讨原发性三叉神经痛（PTN）和疱疹后三叉神经痛（PHN）的临床特征,并比较经卵圆孔射频热凝术（RF-TC）治疗PTN和PHN的临床疗效。方法：随机选取2019年1月至2020年8月在我院治疗的三叉神经痛患者123例,其中原发性三叉神经痛90例,带状疱疹后神经痛33例。所有患者均通过RF-TC进行治疗,治疗后通过视觉模拟量表（VAS）、巴罗神经研究所疼痛强度量表对面部疼痛评分进行疼痛评估,通过巴罗神经研究所麻木评分进行麻木评定,通过健康问卷-9对患者抑郁情况进行评估,通过匹斯堡睡眠质量指数测量患者心理状态。结果：PTN患者发病年龄显著低于PHN患者（P<0.05）,而病程显著高于PHN患者（P<0.05）;PHN患者的眼支发生率高于PTN患者（39.39% vs 8.89%, P<0.05）。两组患者经RF-TC治疗前后VAS评分无显著差异（P>0.05）。PHN组从轻度到重度影响睡眠质量的比例显著高于PTN组（30.30% vs 10.00%, P<0.05）。PTN组患者治疗后中重度抑郁患者比例显著高于PHN组患者（21.11% vs 9.09%, P<0.05）。两组患者经RF-TC治疗后,临床治疗有效率、面麻木程度以及巴罗神经研究所疼痛强度量表评定的面部疼痛无显著差异（P>0.05）。结论：经卵圆孔射频热凝术治疗原发性三叉神经痛和带状疱疹后三叉神经痛是安全有效的,但治疗后疱疹后三叉神经痛失眠的发生率较高,而原发性三叉神经痛的抑郁发生率较高。     

Neuropathic orofacial pain: Cannabinoids as a therapeutic avenue

Neuropathic orofacial pain (NOP) exists in several forms including pathologies such as burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN) and postherpetic neuralgia (PHN). BMS and PIFP are classically diagnosed by excluding other facial pain syndromes. TN and PHN are most often diagnosed based on a typical history and presenting pain characteristics. The pathophysiology of some of these conditions is still unclear and hence treatment options tend to vary and include a wide variety of treatments including cognitive behaviour therapy, anti-depressants, anti-convulsants and opioids; however such treatments often have limited efficacy with a great amount of inter-patient variability and poorly tolerated side effects. Analgesia is one the principal therapeutic targets of the cannabinoid system and many studies have demonstrated the efficacy of cannabinoid compounds in the treatment of neuropathic pain. This review will investigate the potential use of cannabinoids in the treatment of symptoms associated with NOP.     

Varicella zoster virus vaccines: potential complications and possible improvements

Varicella zoster virus(VZV) is the causative agent of varicella(chicken pox) and herpes zoster(shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine(v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia(PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.     

Gabapentin Administration Reduces Reactive Gliosis and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

The lithium-pilocarpine model of epilepsy reproduces in rodents several features of human temporal lobe epilepsy, by inducing an acute status epilepticus (SE) followed by a latency period. It has been proposed that the neuronal network reorganization that occurs during latency determines the subsequent appearance of spontaneous recurrent seizures. The aim of this study was to evaluate neuronal and glial responses during the latency period that follows SE. Given the potential role of astrocytes in the post-SE network reorganization, through the secretion of synaptogenic molecules such as thrombospondins, we also studied the effect of treatment with the α2δ1 thrombospondin receptor antagonist gabapentin. Adult male Wistar rats received 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once SE was achieved, seizures were stopped with 20 mg/kg diazepam. Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days. In vitro experiments were performed in dissociated mixed hippocampal cell culture exposed to glutamate, and subsequently treated with gabapentin or vehicle. During the latency period, the hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis, with increased GFAP and nestin expression. Gliosis intensity was dependent on the Racine stage attained by the animals and peaked 15 days after SE. Microglia was also reactive after SE, and followed the same pattern. Neuronal degeneration was present in SE-animals, and also depended on the Racine stage and the SE duration. Polysialic-acid NCAM (PSA-NCAM) expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals. Gabapentin treatment was able to reduce reactive gliosis, decrease neuronal loss and normalize PSA-NCAM staining in hippocampal CA-1. In vitro, gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity. Our results show that gabapentin treatment during the latency period after SE protects neurons and normalizes PSA-NCAM probably by direct interaction with neurons and glia.     

Analysis of the analgesic effects of tricyclic antidepressants on neuropathic pain,diabetic neuropathic pain,and fibromyalgia in rat models

ObjectiveTo investigate the analgesic effect of amitriptyline on neuropathic pain model rats, diabetic neuropathic pain model rats and fibromyalgia model rats.MethodsThe healthy male Sprague wrote – Dawley (SD) rats were taken as the research object, and they were randomly divided into model group (group A), beside the sciatic nerve and injection of 5 mm amitriptyline group (group B), beside the sciatic nerve and injection of 10 mm amitriptyline group (group C), beside the sciatic nerve and injection of 15 mm amitriptyline group (group D), intraperitoneal injection of amitriptyline group (group E). Pain induced by selective injury of sciatic nerve branches in rats, pain induced by chronic compression of sciatic nerve, diabetic neuropathic pain and fibromyalgia were conducted to determine the pain threshold of mechanical stimulation in rats after drug administration.ResultsThe pain threshold of mechanical stimulation in the local amitriptyline group (group B, C, D) was significantly higher than that in the group A and group E at each time point after drug treatment, and the pain threshold of mechanical stimulation gradually increased with the increase of concentration. There was no statistically significant difference in mechanical stimulation pain threshold between group A and group E at each time point after drug treatment.ConclusionPara-sciatic injection of amitriptyline at different concentrations has analgesic effects on neuropathic pain, diabetic neuropathic pain and fibromyalgia in rat models, and amitriptyline directly ACTS on the local sciatic nerve.     

Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate

Gabapentin is an anticonvulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its antihyperalgesic action remains elusive. This study aims to help delineate gabapentin's antihyperalgesic mechanisms. We assessed the effectiveness of gabapentin at decreasing mechanical and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared the effectiveness of pre‐ or post‐treatment with systemic or intrathecal (i.t.) gabapentin at reducing the development and maintenance of the neuropathic pain symptoms. Gabapentin successfully decreased mechanical and cold hypersensitivity, both as a pretreatment and post‐treatment. Furthermore, both i.t. and systemic administration of gabapentin were effective in reducing the behavioral hypersensitivity; however, the i.t. administration was superior to the systemic. We also examined gabapentin's effects at inhibiting hindpaw formalin‐induced release of excitatory amino acids (EAAs) in the spinal cord dorsal horn (SCDH) both in naïve rats and in rats with neuropathic pain. We present the first evidence that gabapentin reduces the formalin‐induced release of both glutamate and aspartate in SCDH. Furthermore, i.t. gabapentin reduces the enhanced noxious stimulus‐induced spinal release of glutamate seen in neuropathic rats. These data suggest that gabapentin reduces neuropathic pain symptoms by inhibiting the release of glutamate in the SCDH.     

阿米替林对脊髓电刺激治疗幻肢痛疗效的影响

目的：本研究旨在探讨阿米替林干预对脊髓电刺激（SCS）治疗幻肢痛疗效的影响。方法：研究对象为2007年1月至2009年6月在我科行SCS置入术且符合入组标准并自愿参加研究的幻肢痛患者,共获7例。术后SCS均开启,阿米替林治疗在术后1个月时开始。疼痛、情绪、生活质量评估采用视觉模拟评分法（visual analogue scales,VAS法）,现时疼痛强度评分法（presentpain intensity。PPI）,综合性医院焦虑抑郁量表（The Hospital Anxiety and Depression Scale,HAD）,疼痛失能指数（Pain disability index,PDI）。结果：（1）开启SCS后患者的疼痛、抑郁焦虑情绪及生活质量均得到显著改善。（2）所有患者在使用阿米替林治疗以后疼痛、情绪及生活质量也显著改善。结论：阿米替林能显著提高SCS对幻肢痛的疗效。     

The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study

Background

Vaccination against herpes zoster is being considered in many countries. We conducted a multicentre prospective study to describe the impact of herpes zoster and postherpetic neuralgia on health-related quality of life.

Methods

From October 2005 to July 2006, 261 outpatients aged 50 years or older with herpes zoster were recruited from the clinical practices of 83 physicians within 14 days after rash onset. The Zoster Brief Pain Inventory was used to measure severity of pain and interference with activities of daily living because of pain. The EuroQol EQ-5D assessment tool was used to measure quality of life. These outcomes were assessed at recruitment and on days 7, 14, 21, 30, 60, 90, 120, 150 and 180 following recruitment.

Results

Acute herpes zoster interfered in all health domains, especially sleep (64% of participants), enjoyment of life (58%) and general activities (53%). The median duration of pain was 32.5 days. The median duration of interference with activities of daily living because of pain varied between 27 and 30 days. Overall, 24% of the participants had postherpetic neuralgia (pain for more than 90 days after rash onset). Anxiety and depression, enjoyment of life, mood and sleep were most frequently affected during the postherpetic neuralgia period. The mean EQ-5D score was 0.59 at enrolment and remained at 0.67 at all follow-up points among participants who reported clinically significant pain.

Interpretation

These data support the need for preventive strategies and additional early intervention to reduce the burden of herpes zoster and postherpetic neuralgia.Herpes zoster, which is characterized by dermatomal pain and vesicular rash,^1,2 results from reactivation of the varicella-zoster virus.^3,4 The average lifetime risk of herpes zoster in developed countries is estimated to be about 30%^5–7 and increases with increasing life expectancy. The most common complication of herpes zoster, and one of the most challenging to treat, is postherpetic neuralgia, a painful condition often defined as pain persisting for more than 90 days after rash onset.⁸ According to this definition, postherpetic neuralgia is estimated to occur in 8%–27% of people with herpes zoster overall.^9–14 The risk of postherpetic neuralgia increases markedly with age.¹⁵The Shingles Prevention Study, a randomized double-blind placebo-controlled trial, showed that a live-attenuated varicella-zoster virus vaccine was safe and effective in preventing herpes zoster and postherpetic neuralgia among people 60 years of age and older.¹³ Given these promising results, policy-makers and clinicians are being asked to make recommendations regarding the use and funding of the herpes zoster vaccine. To do this, evidence on the burden of herpes zoster from the patient’s perspective is required. The only data available on the impact of herpes zoster on health-related quality of life comes from two short-term studies.^16,17 Clinical reports and cross-sectional surveys^18–20 have also suggested that postherpetic neuralgia can profoundly impair quality of life. However, no study followed a cohort of patients with newly diagnosed herpes zoster for a sufficient period to assess postherpetic neuralgia and describe the associated impact on quality of life.We undertook a multicentre prospective study to describe the impact of herpes zoster and postherpetic neuralgia on health-related quality of life.     

The effect of gabapentin and phenytoin on sperm-morphology in Wistar rats

The objective of the present study was to investigate the effects of the antiepileptic drugs, gabapentin and phenytoin, on sperm morphology in Wistar rats. Groups (n=5) of rats were treated with cyclophosphamide (20 mg/day), gabapentin (16, 25, 32 mg/day) and phenytoin (3.5, 5.5, 7 mg/day) for five consecutive days. 14 and 35 days after the last exposure, sperm morphology was evaluated by standard procedure. Gabapentin and phenytoin did not induce significant changes in sperm morphology. The results suggest that phenytoin and gabapentin are not germ cell mutagens in males, and do not appear to adversely affect male fertility.     

A method for bulbospinal trigeminal nucleotomy in the treatment of facial deafferentation pain

Many types of facial pain are difficult to treat, such as postherpetic, posttraumatic, or pain following denervation procedures used in the treatment of trigeminal neuralgia (anesthesia dolorosa), all of which involve deafferentation of the spinal trigeminal nucleus.     

Dorsal root entry zone lesions in the treatment of pain following brachial plexus avulsion, spinal cord injury and herpes zoster

This paper details the long-term results in patients treated with dorsal root entry zone (DREZ) lesions for the treatment of pain following brachial plexus avulsion, spinal cord injury, and herpes zoster. With our current operative technique, 82% of patients with brachial plexus avulsion injuries were afforded long-term pain relief. Patients with pain confined to dermatomes just below the level of spinal injury also did well with DREZ lesions, although the results were less good in patients with diffuse pain or with sacral pain. The postoperative results in patients with postherpetic pain were disappointing.