Chinese Association for the Study of Pain:Experts consensus on ultrasound-guided injections for the treatment of spinal pain in China(2020 edition)

Spinal pain(SP)is a common condition that has a major negative impact on a patient’s quality of life.Recent developments in ultrasound-guided injections for the treatment of SP are increasingly being used in clinical practice.This clinical expert consensus describes the purpose,significance,implementation methods,indications,contraindications,and techniques of ultrasound-guided injections.This consensus offers a practical reference point for physicians to implement successfully ultrasound-guided injections in the treatment of chronic SP.

Differences between the healthcare systems of Quebec and France for the treatment of pain due to spinal disorders

In Quebec,Canada,the public healthcare system offers free medical services.However,patients with spinal pain often encounter long waiting times for specialist appointments and limited physiotherapy coverage.In contrast,private clinics provide expedited care but are relatively scarce and entail out-of-pocket expenses.Once a patient with pain caused by a spinal disorder meets a pain medicine specialist,spinal intervention is quickly performed when indicated,and patients are provided lifestyle advice.Transforaminal epidural steroid injections are frequently administered to patients with radicular pain,and steroid injections are administered on a facet joint to control low back or neck pain.Additionally,medial branch blocks are performed prior to thermocoagulation.France’s universal healthcare system ensures accessibility at controlled costs.It emphasizes physical activity and provides free physical therapy services.However,certain interventions,such as transforaminal and interlaminar epidural injections,are not routinely used in France owing to limited therapeutic efficacy and safety concerns.This underutilization may be a potential cause of chronic pain for many patients.By examining the differences,strengths,and weaknesses of these two systems,valuable insights can be gained for the enhancement of global spinal pain management strategies,ultimately leading to improved patient outcomes and satisfaction.

Effect of microenvironment modulation on stem cell therapy for spinal cord injury pain

Spinal cord injury （SCI） currently ranks second after mental retarda- tion among neurological disorders in terms of cost to society. Pain is a debilitating consequence of SCI related to the nature of the lesion, neurological structures damaged, and secondary pathophysiological changes of surviving tissues （Yezierski, 2005; D＇Angelo et al., 2013）.

The hypothalamic-spinal dopaminergic system:a target for pain modulation

Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise,among others, noradrenergic, serotonergic, γ-aminobutyric acid(GABA)ergic, and dopaminergic fibers.The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood.The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.

Proteomic analysis of the dorsal spinal cord in the mouse model of spared nerve injury-induced neuropathic pain

Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury（SNI）-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry（MS/MS）. After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain,and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.

Effects of morphine and electroacupuncture on substance P level in spinal cord and their relation to pain threshold in rats

Immunoreactive substance P(Ir-SP)level,and substance P likeimmunoreactivity(SP-Li)in the spinal cord were observed with radioimmunoassay andimmunohistochemistry in rats after they were given an intraperitoneal injection of mor-phine(7.5mg/kg)or electroacupunctured(3V and 3Hz)on the “Jiaji point”.It wasfound that the pain threshold(PT),Ir-SP level and SP-Li in the dorsal horn of the spi-nal cord were more significantly increased in the animals after the administration ofmorphine or electroacupuncture than in the control(P【0.05～0.01).The combined effectsof morphine and electropacupuncture were even more powerful than either of the agentswas administered singly.Naloxone could block the analgesic effect and the elevation ofIr-SP due to morphine or electroacupuncture.The findings suggest that there is a synergismbe tween morphine and electroacupuncture and the analgesic effect of the 2 depends uponthe increase of Ir-SP level of the spinal cord mediated through the opiate receptors.

Orofacial inflammatory pain affects the expression of MT1 and NADPH-d in rat caudal spinal trigeminal nucleus and trigeminal ganglion

Very little is known about the role of melatonin in the trigeminal system, including the function of melatonin receptor 1. In the present study, adult rats were injected with formaldehyde into the right vibrissae pad to establish a model of orofacial inflammatory pain. The distribution of melatonin re- ceptor 1 and nicotinamide adenine dinucleotide phosphate diaphorase in the caudal spinal trigeminal nucleus and trigeminal ganglion was determined with immunohistochemistry and histo- chemistry. The results show that there are significant differences in melatonin receptor 1 expression and nicotinamide adenine dinucleotide phosphate diaphorase expression in the trigeminal ganglia and caudal spinal nucleus during the early stage of orofacial inflammatory pain. Our findings sug- gest that when melatonin receptor 1 expression in the caudal spinal nucleus is significantly reduced, melatonin＇s regulatory effect on pain is attenuated.

Low-dose radiation on spinal cord might be a new therapy for intractable chronic cancer and non-cancer pain

Intractable chronic pain is a great challenge in clinic.Central sensitization based on the positive changes of dendritic spines is the main mechanism of intractable chronic pain.And low-dose radiation has been proved to regulate the changes of dendritic spines negatively.Hence,we make a hypothesis that low-dose radiation could relieve cancer and noncancer pain through negatively regulating the shape and reducing the number and density of dendritic spines in the spinal cord.This method is supposed to be a new therapy for intractable chronic pain by expanding indication to non-cancer pain,translocating radiation site from where the tumor exists to special segments of spinal cord and keeping radiation dose at a low level.This therapy would be reliable for relieving non-cancer pain and supply more choices for relieving cancer pain.

Topographical Anatomical Neuropathic-Pain Guided (TANG) Mapping: A Tool Derived from a Patient Perspective to Facilitate the Transition from Spinal Cord Stimulator Trial to Potential Permanent Implantation

Introduction: Collecting a patient’s pain scores and the analgesic effect achieved during spinal cord stimulation (SCS) trials can be difficult, and no standard exists for doing so. We propose a topographical mapping tool that was derived from a patient’s perspective. Case: A 60-year-old man with postherpetic neuralgia (PHN) underwent a SCS trial after conservative treatment failed to relieve his pain. During the SCS trial, with the SCS off and on in five different settings, he recorded pain levels in each of the six different painful zones he identified. The data collected were transferred to a topographical and anatomical map, which helped the physicians to better understand the effects of the SCS at different settings. Ultimately, the data collected by the patient helped the physicians to implant a permanent SCS successfully. Conclusions: Patient pain diaries have been used in pain medicine for years. This particular patient’s collection of pain scores and SCS effects inspired the construction of a more standardized tool for collecting such data during SCS trials. We propose that use of our Topographical Anatomical Neuropathic-pain Guided (TANG) mapping tool will enable physicians to choose SCS lead positions more precisely than is currently possible.

Acetylcholine participates in pain modulation by influencing endogenous opiate peptides in rat spinal cord

The spinal cord is a necessary pathway that transfers the body nociceptive inputs to the brain, and endo-genous opiate peptides (EOP) play an important role in pain modulation. Our previous work has proven that arginine vasopressin (AVP) antinociception in the caudate nucleus (CdN) relates with the acetylcholine (Ach) system mainly. The communication was de-signed to investigate the interrelations between Ach system and EOP system at the spinal level during pain process. The results showed that: 1) pain stimulation increased L-enkephalin (L-Ek), β-endorphin (β-Ep), dynorphin A1-13(DynA1-13), Ach and choline (Ch, an Ach metabolic product) concentrations in the spinal cord;2) Ach increased L-Ek, β-Ep and DynA1-13 concentrations in the spinal cord;and 3) Atropine (M-receptor inhibitor) or hexahydric gallamine (N-receptor inhibitor) decreased L-Ek, β-Ep and DynA1-13 concentrations in the spinal cord. The data suggested that Ach antinociception was involved in the EOP system at the spinal level.

Epidural Blood Patch for Treatment of Postdural Puncture Headache in a Patient with Spinal Fusion and Recent Implantation of Intrathecal Pain Pump

We present an interesting case report of a 49-year-old female who presented with symptoms of post-dural puncture headache following implantation of an intrathecal pain pump. Her history was complicated by previous multi-level spinal fusion with hardware. The patient was evaluated and felt to be a candidate for epidural blood patch, which she elected to proceed with. Under fluoroscopic guidance epidural blood patch was successfully performed. Immediately following the procedure the patient noted significant improvement in the headache and six hours following the procedure was headache free and remained so at follow up three weeks later.

Spinal Cord Stimulation (SCS) for Pain Control in a Quadriplegic Patient: A Case Report

Background: There are reports of pain relief from spinal cord stimulation (SCS) in patients with incomplete spinal cord injuries. However, the results for pain relief from SCS in patients with complete spinal cord injury are dismal. Patients with complete spinal cord injury therefore are generally not considered suitable candidates for SCS. The authors report a case in which a quadriplegic patient with cervical spinal cord injury got significant pain relief from spinal cord stimulation. Methods: The patient is 41 years old with quadriplegia secondary to C5-6 injury. He has no function below the level of the injury except for a few patchy areas of sensation. Ten years after the injury the patient had hemorrhoidectomy. This resulted in severe pain in the anal pain. The treatment for pain failed conservative treatment. He however did have good response to a trial of spinal cord stimulation through an epidural lead placed at T8-T9 vertebral body level. Permanent implantation of spinal cord stimulator was therefore performed. Results: At preoperative evaluation the patient rated his pain as a 7/10. Presently at 2 years’ follow-up the patient rates his pain at 1/10. Conclusions: Spinal cord stimulation proved to be a successful means of achieving adequate pain relief in a patient who had complete loss of motor function below the level of the injury. Therefore, although patients with such condition are unlike to benefit from SCS it is worthwhile trying this treatment if no other option is available there.

Spinal processing of bee venom-induced pain and hyperalgesia

Subcutaneous injection of bee venom causes long-term neural activation and hypersensitization in the dorsal horn of the spinal cord,which contributes to the development and maintenance of various pain-related behaviors.The unique behavioral 'phenotypes' of nociception and hypersensitivity identified in the rodent bee venom test are believed to reflect a complex pathological state of inflammatory pain and might be appropriate to the study of phenotype-based mechanisms of pain and hyperalgesia.In this review,the spinal processing of the bee venom-induced different 'phenotypes' of pain and hyperalgesia will be described.The accumulative electrophysiological,pharmacological,and behavioral data strongly suggest that different 'phenotypes' of pain and hyperalgesia are mediated by different spinal signaling pathways.Unraveling the phenotype-based mechanisms of pain might be useful in development of novel therapeutic drugs against complex clinic pathological pain.

An Analysis of Pain Following Traumatic Spinal Cord Injury among Adults in Zimbabwe

The purpose of the study was to analyse on pain following traumatic spinal cord injury, its prevalence, the types of pain present, the common treatments used and their perceived effectiveness in the management of these reported pain types. A cross sectional study was carried out at St Giles Rehabilitation Centre and from members of the Spinal Injuries Association of Zimbabwe (SIAZ). A researcher-administered questionnaire was used to collect data from 24 participants with traumatic spinal cord injury. The questionnaire elicited information on demographic data, pain characteristics and the perceived effectiveness of the common treatments used. Among the 24 participants in the study, 17 were males (70.8%) and 7 were females (29.2%). Pain prevalence was 79.2% among the study participants and approximately a fifth (21.03%) of all participants rated their pain as severe. Eight (33.3%) of the participants had neuropathic pain while 11 (45.8%) had both nociceptive and neuropathic pain types. However, no association was found between sex, age, time post injury when tested against the presence of pain (p > 0.05). Weather changes aggravated almost every type of pain reported. Both pharmacological and non-pharmacological methods were used to manage the pain but their perceived effectiveness was rated as low. The majority of the traumatic spinal cord injured people experienced some pain and this pain was severe in a fifth of all participants. Pain significantly affected their quality of life. Physiotherapists and other medical professionals need to be aware of this and should employ pain reducing modalities and empathy when dealing with these patients.

Combined Sacral Nerve Roots Stimulation and Low Thoracic Spinal Cord Stimulation for the Treatment of Chronic Pelvic Pain

Some pelvic pain syndromes are very resistant to medical treatment. Several studies have demonstrated that sacral neuromodulation, which has been successfully used for the treatment of bladder dysfunction, incontinence, urinary retention and urinary frequency [1]-[3], can be successfully used for the treatment of chronic pelvic pain [4]-[7]. Several studies have also demonstrated significant involvement of dorsal column pathways in the transmission of visceral pelvic pain [8] and the successful use of spinal cord stimulation for the treatment of chronic pelvic pain [9]. We report three cases of severe chronic pelvic pain that failed conservative treatment modalities. Placement of a combined sacral nerve roots stimulator and a low thoracic spinal cord stimulator resulted in a significant pain relief and improvement in daily life activities. We believe that this combination may help patients suffering from chronic pelvic pain resistant to medical management.

Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.

脊髓电刺激治疗痛性周围神经病的现状和进展

痛性周围神经病是以神经病理性疼痛为突出表现的周围神经病。脊髓电刺激通过脉冲电流刺激脊髓神经,阻断疼痛信号的传递。脊髓电刺激已被用于包括痛性周围神经病在内的多种神经系统疾病,并广泛用于临床。该研究就脊髓电刺激镇痛的基本机制、在痛性周围神经病的临床应用价值以及该技术的最新进展展开论述。

SURGICAL TREATMENT OF METASTATIC SPINAL TUMOR

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运动神经损伤早期脊髓Calpain-2的上调促进IL-6的异常表达

【目的】探讨L5前根切除损伤运动神经的慢性痛模型中早期脊髓内钙依赖性蛋白水解酶Calpain-2(CALP2)介导白细胞介素-6(IL-6)异常表达的病理生理。【方法】采用免疫荧光组织化学和蛋白免疫印迹法,观察L5-VRT后L5背根、脊髓内CALP2的表达改变以及术前预处理calpain抑制剂MDL28170对脊髓内L5-VRT诱导的IL-6异常表达的影响,同时观察单纯给予外源性CALP2(rat recombinant calpain-2,rr-CALP2)对正常大鼠脊髓内IL-6表达的影响。【结果】(1)L5-VRT诱导邻近L5背根以及脊髓背角和前角内钙依赖性蛋白酶CALP2表达升高;(2)通过术前预处理calpain抑制剂MDL28170(25 mg/kg)部分阻断L5-VRT诱导的双侧脊髓IL-6异常表达;(3)在正常大鼠单侧L5背根表面给予rr-CALP2可直接诱导双侧脊髓IL-6蛋白水平升高。【结论】运动神经损伤早期可能首先通过损伤处CALP2的激活,诱导脊髓IL-6异常表达,参与慢性痛的产生。

Formalin-induced astrocyte glutamate-glutamine cycle involved in rat spinal cord central sensitization

BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyperalgesia and neuropathic pain. Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood. OBJECTIVE： To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Orthopedics, Second Hospital, Lanzhou University, China from September 2007 to August 2008. MATERIALS： Methionine sulfoximine （MSO, 0.1 mmol/L）, glutamine （0.25 mmol/L）, and formalin were used for this study. METHODS： A total of 43 male, Sprague Dawley rats, aged 4 months, were randomly assigned to a sham operation group （n = 6） and a model group （n = 37）. Rats in the model group received intrathecal infusion in the spinal cord. 7 days later, 37 model rats were randomly divided into PBS, MSO, glutamine, MSO ＋ glutamine and formalin subcutaneous injection alone groups. The PBS, MSO, glutamine, MSO ＋ glutamine groups were respectively intrathecally injected with PBS, MSO, glutamine, MSO ＋ glutamine （50 μL each）, and then infused with 10 μL of saline. Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord. At 15 minutes after intrathecal injection, a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5% formalin （50 μL） in the left hindpaw. MAIN OUTCOME MEASURES： Changes in spontaneous nociceptive behavior （licking/biting or flinching） were observed following formalin injection into the rat hindpaw. RESULTS： Compared with the PBS group, duration of licking/biting was significantly shortened, and flinching frequency was significantly diminished in the MSO group （P 〈 0.05）. Compared with the MSO group, duration of licking/biting was significantly prolonged, and flinching frequency was significantly increased in the MSO ＋ glutamine group （P 〈 0.05）. There was no significant difference in inflammatory pain behaviors among the sham operation, PBS, glutamine, MSO ＋ glutamine, and formalin subcutaneous injection alone groups （P 〉 0.05）. CONCLUSION： The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.