Genetic Evidence for Causal Association Between Hypertension and Chronic Pain:A Bidirectional Two-Sample Mendelian Randomization Study

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.

Reconstructive surgery for phantom and residual limb pain in post-conflict settings

Traumatic amputations remain one of the most frequent and disturbing wounds of armed conflict.In this scenario,most amputees develop residual and phantom limb pain,impacting their quality of life.There are several elective surgical procedures available for both conditions,such as neuroma excision followed by nerve reconstruction,nerve relocation,e.g.,surgically implanting a transected nerve into a muscle,nerve transfers in cases of associated paralysis,and most recently,regenerative peripheral nerve interface surgery.Whenever possible in the post-conflict phase,a coordinated effort between traveling humanitarian surgeons specializing in reconstructive microsurgery and local healthcare providers is essential for successfully treating phantom and chronic residual limb pain in post-conflict amputees.While providing a detailed logistical framework for global humanitarian missions is beyond the scope of this article,we provide a brief perspective on a topic of utmost importance for reconstructive surgeons worldwide:the high-quality care and treatment of refugees and those whose lives have been impacted by conflict,disaster,or displacement.

Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient:A case report

BACKGROUND Supernumerary phantom limb(SPL)sensation is the experience of additional limbs,either single or a pair of limbs.Unique to traumatic spinal cord injuries,we report effect of transcranial direct current stimulation(tDCS)on SPL pain in a patient with cervical cord injury.CASE SUMMARY The subject was a 57-year-old man who was diagnosed with complete spinal cord injury(C6/C5,motor level;C5/C5,sensory level;AIS-A)approximately three months ago.After a period of 2 wk,we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 mA.Following that treatment,the patient experienced a decrease of SPL pain intensity and frequency,which lasted for 1 week after the end of treatment.CONCLUSION Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

Ultrasound-Guided Superior Gluteal Nerve Hydrodissection in the Treatment of Deep Gluteal Syndrome

Background: Deep gluteal syndrome is a common cause of posterior hip pain. It results from peripheral nerves, such as the sciatic or superior gluteal nerve, being compressed in the deep gluteal space. Hydrodissection is a novel technique for the treatment of nerve pain due to entrapment. The use of hydrodissection for the treatment of deep gluteal syndrome has not been reported. Methods: A case report involved a 42-year-old female presenting with deep gluteal syndrome. Case report: We report, with patient consent, an ultrasound-guided superior gluteal nerve hydrodissection method used for treating the deep gluteal syndrome. A previously healthy 42-year-old female patient sought medical attention due to persistent left gluteal pain. Trials of joint injections, physiotherapy, and epidural blocks were unsuccessful. Hydrodissection under ultrasound-guidance allowed separation of the fascial plane in areas with significant neural innervation. We targeted the superior gluteal nerve with hydrodissection offering the patient immediate and persistent relief from her symptoms. Conclusion: Ultrasound-guided hydrodissection of the superior gluteal nerve offers an effective and novel diagnostic and treatment option for deep gluteal syndrome.

Central nervous system stimulation therapies in phantom limb pain:a systematic review of clinical trials

Phantom limb pain is a chronic pain syndrome that is difficult to cope with.Despite neurostimulation treatment is indicated for refractory neuropathic pain,there is scant evidence from randomized controlled trials to recommend it as the treatment choice.Thus,a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain.A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases.Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed.There were a total of 10 full-text articles retrieved and included in this review.Deep brain stimulation,repetitive transcranial magnetic stimulation,transcranial direct current stimulation,and motor cortex stimulation were the treatment strategies used in the selected clinical trials.Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception,as well as to relieve anxiety and depression symptoms in phantom limb pain patients.Conversely,invasive approaches were considered the last treatment option as evidence in deep brain stimulation and motor cortex stimulation suggests that the value of phantom limb pain treatment remains controversial.However,the findings on use of these treatment strategies in other forms of neuropathic pain suggest that these invasive approaches could be a potential option for phantom limb pain patients.

Professor Liu Guobin used traditional Chinese medicine to cure a case of primary erythema limb pain

Primary erythema limb pain is a very rare disease,and its pathogenesis is not clear.Usually,the pain symptoms of patients exist for a long time,which seriously affect the daily life of patients and increase the economic burden of patients.Professor Liu Guobin,who has been engaged in the diagnosis and treatment of peripheral vascular diseases for nearly 30 years,believes that heat-toxin and blood stasis collaterals are closely related to the disease,and emphasizes the principle of heat-toxin and evil qi causing the disease.It is emphasized that clearing heat and detoxification,promoting blood circulation and dispersing blood stasis are the main treatment principles.This paper selects a typical case to describe Professor Liu's clinical experience in the treatment of primary erythema limb pain by oral and external use of traditional Chinese medicine,so as to provide an effective method of traditional Chinese medicine for the treatment of primary erythema limb pain.

全息针法对幻肢痛的治疗体会

幻肢痛(phantom limb pain,PLP)多发于残障人士,发病率高但无特效药物或治疗手段,是社会痛点。刘红梅医师基于中医“脑为元神之府”理念,结合大量临床病例观察,认为幻肢痛性质属寒属虚,病位在脑,与经络感传密切相关,治疗上选择全息针法脐针,重视幻肢热感感传与幻经络“气至病所”,多获良效。现介绍刘红梅医师在应用全息针法治疗幻肢痛过程中发现的值得思考的临床现象以及临床心得体会。

Cortical plasticity and nerve regeneration after peripheral nerve injury

With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.

Pharmacological interventions for phantom limb pain

Objective To review the mechanisms and current clinical application of pharmacological interventions for phantom limb pain. Data sources Both Chinese and English language literatures were searched using MEDLINE （1982-2011）, Pubmed （1982-2011） and the Index of Chinese Language Literature （1982-2011 ）. Study selection Data from published articles about pharmacological management of phantom limb pain in recent domestic and foreign literature were selected. Data extraction Data were mainly extracted from 96 articles which are listed in the reference section of this review. Results By reviewing the mechanisms and current clinical application of pharmacological interventions for phantom limb pain, including anticonvulsants, antidepressants, local anaesthetics, N-methyI-D-aspartate receptor antagonists, non-steroidal anti-inflammatory drugs, tramadol, opioids, calcitonin, capsaicin, beta-adrenergic blockers, clonidine, muscle relaxants, and emerging drugs, we examined the efficacy and safety of these medications, outlined the limitations and future directions. Conclusions Although there is lack of evidence-based consensus guidelines for the pharmacological management of phantom limb pain, we recommend tricyclic antidepressants, gabapentin, tramadol, opioids, local anaesthetics and N-methyI-D-aspartate receptor antagonists as the rational options for the treatment of phantom limb pain.

transcranial Direct Current Stimulation (tDCS) for the treatment and investigation of Phantom Limb Pain (PLP)

Phantom limb pain(PLP)is a complex medical condition that is often difficult to treat,and thus can become detrimental to patients’quality of life.No standardized clinical treatments exist and there is no conclusive understanding of the underlying mechanisms causing it.Noninvasive brain stimulation(NIBS)has been used to find correlations between changes in brain activity and various brain conditions,including neurological disease,mental illnesses,and brain disorders.Studies have also shown that NIBS can be effective in alleviating pain.Here,we examined the literature on a particular type of NIBS,known as transcranial direct current stimulation(tDCS),and its application to the treatment of PLP.We first discuss the current hypotheses on the working mech-anism of tDCS and then we examine published evidence of its efficacy to treat PLP.We conclude this article by discussing how tDCS alone,and in combination with brain imaging techniques such as electroencephalography(EEG)and magnetic resonance imagining,could be applied to further investigate the mechanisms underlying PLP.

DESIGNING A FEASIBILITY STUDY ON THE USE OF ACUPUNCTURE FOR PHANTOM LIMB PAIN

People with diabetes are 30 times more likely to undergo amputation than the general population.A total of 3.2million people in the UK have been diagnosed with diabetes and by 2025 this number is estimated to be 5million.One potential complication post amputation is phantom limb pain(PLP),a prevalent and often chronic condition which is difficult to treat.To inform a

A review of pain outcomes following targeted muscle reinnervation in lower extremity limb pain

Approximately 75%experience phantom(PLP),residual(RLP),or general(GLP)limb pain following lower extremity amputation.Targeted muscle reinnervation(TMR)is a peripheral nerve transfer that reroutes amputated nerves to motor endplates that can prevent or treat limb pain.This systematic review summarizes pain outcomes following primary and secondary treatment of lower extremity PLP,RLP,and GLP.Primary literature review of three databases-PubMed,EMBASE,MEDLINE-were used for all articles related to TMR and lower extremity limb pain,querying the same keywords:“targeted muscle reinnervation”AND“pain”.Citations were then reviewed and eliminated if only upper extremities were studied or the study lacked pain outcomes.Citations were categorized as primary or secondary TMR.Pain outcomes,including Numerical Rating Scales(NRS)and Patient-Reported Outcome Measurement Information System(PROMIS)Pain scores,were aggregated when appropriate.Ten studies met all inclusion and exclusion criteria after formal review for a total of 431 extremities,of which 79.1%(n=341 limbs)were lower extremities.Average primary TMR PROMIS scores for PLP and RLP were lower than amputees without primary TMR.Average NRS scores and PROMIS Pain scores in secondary TMR demonstrated improvements in PLP,RLP,and GLP.Primary and Secondary TMR does prevent and improve PLP,RLP,and GLP;however,a minority of studies report quantifiable pain outcomes.All future TMR studies should include validated pain outcomes to better quantify the expected pain and quality of life improvements after lower extremity TMR.

Efficacy of targeted muscle reinnervation for treating and preventing postamputation pain-a systematic review

Aim:Targeted muscle reinnervation(TMR)is a procedure pioneered to improve control of myoelectric prostheses and was fortuitously found to improve postamputation pain by transferring residual nerve ends from an amputated limb to reinnervate motor nerve units in denervated muscles.This study sought to perform a systematic review of the literature regarding the postamputation pain-related outcomes following TMR.Methods:PubMed database was queried using the key term“targeted muscle reinnervation”.Articles were chosen based on the following criteria:(1)clinical studies on TMR;(2)greater than one subject;(3)studies were case-controls,comparative cohort analyses,controlled trials,or randomized controlled trials;and(4)studies included one or more outcomes of interest:prosthetic use and functionality,improvement or persistence of pain,indications,complications,donor nerves,and technical aspects of TMR.Results:Overall,9 studies including 101 upper extremity and 252 lower extremity nerve transfers were analyzed,with nerve transfer type,amputation location,and specific neurotizations reported.Four studies assessed the efficacy of TMR in addressing phantom limb pain(PLP)and residual limb pain(RLP),with 3 out of 4 studies reporting significant improvements in PROMIS(Patient Reported Outcome Measurement Information System)scores in TMR subjects compared to controls.Five additional studies did not analyze PROMIS scores but reported subjective improvements in pain outcomes.Conclusion:Included studies demonstrated TMR had lower maximal pain and pain intensity,behavior and interference compared to the standard of care.Secondary TMR used to treat patients with established painful neuromas also reported improvement in pain compared to baseline.

Advances in upper limb loss rehabilitation:the role of targeted muscle reinnervation and regenerative peripheral nerve interfaces

Upper limb loss results in significant physical and psychological impairment and is a major financial burden for both patients and healthcare services.Current myoelectric prostheses rely on electromyographic(EMG)signals captured using surface electrodes placed directly over antagonistic muscles in the residual stump to drive a single degree of freedom in the prosthetic limb(e.g.,hand open and close).In the absence of the appropriate muscle groups,patients rely on activation of biceps/triceps muscles alone(together with a mode switch)to control all degrees of freedom of the prosthesis.This is a non-physiological method of control since it is non-intuitive and contributes poorly to daily function.This leads to the high rate of prosthetic abandonment.Targeted muscle reinnervation(TMR)reroutes the ends of nerves in the amputation stump to nerves innervating“spare”muscles in the amputation stump or chest wall.These then become proxies for the missing muscles in the amputated limb.TMR has revolutionised prosthetic control,especially for high-level amputees(e.g.,after shoulder disarticulation),resulting in more intuitive,fluid control of the prosthesis.TMR can also reduce the intensity of symptoms such as neuroma and phantom limb pain.Regenerative peripheral nerve interface(RPNI)is another technique for increasing the number of control signals without the limitations of finding suitable target muscles imposed by TMR.This involves wrapping a block of muscle around the free nerve ending,providing the regenerating axons with a target organ for reinnervation.These RPNIs act as signal amplifiers of the previously severed nerves and their EMG signals can be used to control prosthetic limbs.RPNI can also reduce neuroma and phantom limb pain.In this review article,we discuss the surgical technique of TMR and RPNI and present outcomes from our experience with TMR.