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The Journal of Pain Mar 2024Postamputation pain is currently managed unsatisfactorily with neuron-targeted pharmacological and interventional therapies. Non-neuronal pain mechanisms have emerged as...
Postamputation pain is currently managed unsatisfactorily with neuron-targeted pharmacological and interventional therapies. Non-neuronal pain mechanisms have emerged as crucial factors in the development and persistence of postamputation pain. Consequently, these mechanisms offer exciting prospects as innovative therapeutic targets. We examined the hypothesis that engaging mesenchymal stem cells (MSCs) would foster local neuroimmune interactions, leading to a potential reduction in postamputation pain. We utilized an ex vivo neuroma model from a phantom limb pain patient to uncover that the oligodeoxynucleotide IMT504 engaged human primary MSCs to promote an anti-inflammatory microenvironment. Reverse translation experiments recapitulated these effects. Thus, in an in vivo rat model, IMT504 exhibited strong efficacy in preventing autotomy (self-mutilation) behaviors. This effect was linked to a substantial accumulation of MSCs in the neuroma and associated dorsal root ganglia and the establishment of an anti-inflammatory phenotype in these compartments. Centrally, this intervention reduced glial reactivity in the dorsal horn spinal cord, demonstrating diminished nociceptive activity. Accordingly, the exogenous systemic administration of MSCs phenocopied the behavioral effects of IMT504. Our findings underscore the mechanistic relevance of MSCs and the translational therapeutic potential of IMT504 to engage non-neuronal cells for the prevention of postamputation pain. PERSPECTIVE: The present study suggests that IMT504-dependent recruitment of endogenous MSCs within severely injured nerves may prevent post-amputation pain by modifying the inflammatory scenario at relevant sites in the pain pathway. Reinforcing data in rat and human tissues supports the potential therapeutic value of IMT504 in patients suffering postamputation pain.
PubMed: 38484854
DOI: 10.1016/j.jpain.2024.03.004 -
Anesthesia and Analgesia Mar 2024The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both...
Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.
BACKGROUND
The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis.
METHODS
In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC.
RESULTS
The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667.
CONCLUSIONS
Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.
PubMed: 38478876
DOI: 10.1213/ANE.0000000000006833 -
Strahlentherapie Und Onkologie : Organ... Mar 2024Complex visual hallucinations are rarely seen in neurooncology. They are commonly observed alongside psychotic symptoms in schizophrenia or dementia, in Parkinson's or...
PURPOSE
Complex visual hallucinations are rarely seen in neurooncology. They are commonly observed alongside psychotic symptoms in schizophrenia or dementia, in Parkinson's or Lewy-body disease, after opioid medications or anesthesia, and, in particular, they appear with visual impairments.
METHODS
Here we report two normal-sighted and mentally healthy patients with unusual visual hallucinations after the resection and irradiation of brain metastases, the main features of which were persistent colorful and meaningful images with hallucinatory perseveration.
RESULTS
These cases demonstrate the occurrence of complex visual hallucinations after resection of visual cortices as an effect of deafferentation, so-called visual release hallucinations or phantom images, similar to phantom pain after amputation of a limb.
CONCLUSION
This case serves to heighten awareness in the radiooncology practitioner of the occurrence of visual release hallucinations (Charles Bonnet syndrome) related to multidisciplinary treatment of brain metastases.
PubMed: 38453698
DOI: 10.1007/s00066-024-02213-x -
Cureus Feb 2024Extremity amputations are associated with pain in both the residual limb and the phantom limb. This pain, which is often debilitating, may be prevented by excellent...
Ultrasound-Guided Percutaneous Cryoneurolysis for Perioperative Analgesia Following Major Lower Extremity Amputation: A Randomized, Participant- and Observer-Masked, Sham-Controlled Pilot Study.
BACKGROUND
Extremity amputations are associated with pain in both the residual limb and the phantom limb. This pain, which is often debilitating, may be prevented by excellent perioperative pain control. Ultrasound-guided percutaneous cryoneurolysis is an analgesic modality offering pain control for weeks or months following surgery. This treatment has not been compared to the sham procedure for large nerves (e.g., femoral and sciatic) to provide preoperative analgesia. We therefore conducted a randomized, controlled pilot study to evaluate the use of this modality for the treatment of pain following amputation to (1) determine the feasibility of and optimize the study protocol for a subsequent definitive clinical trial; and (2) estimate analgesia and opioid reduction within the first postoperative weeks.
METHODS
A convenience sample of seven patients undergoing lower extremity amputation were randomized to receive either active cryoneurolysis or a sham procedure targeting the sciatic and femoral nerves in a participant-masked fashion. This was a pilot study with a relatively small number of participants, and therefore the resulting data were not analyzed statistically.
RESULTS
Compared to the participants who received sham treatment (n=3), those who underwent active cryoneurolysis (n=4) reported lower pain scores and decreased opioid consumption at nearly all time points between days one and 21 following amputation.
CONCLUSIONS
Ultrasound-guided percutaneous cryoneurolysis of the femoral and sciatic nerves prior to lower extremity amputation appears feasible and potentially effective. The data from this pilot study may be used to power a definitive randomized clinical trial.
PubMed: 38445120
DOI: 10.7759/cureus.53563 -
Journal of Plastic, Reconstructive &... Apr 2024Targeted muscle reinnervation (TMR) was developed to improve myoelectric prosthesis control for amputees; however, it has become an area of interest in pain modulation....
AIM
Targeted muscle reinnervation (TMR) was developed to improve myoelectric prosthesis control for amputees; however, it has become an area of interest in pain modulation. Evidences indicate that this procedure alleviates chronic pain in amputees. The primary objective of this study was to use social media analysis to understand patients' post-operative pain, satisfaction, and recovery time after TMR.
METHODS
Data were collected from one Facebook group via posts and comments referencing TMR. Posts published between January 1, 2020, and March 24, 2023 were analyzed. Data collected included pain prior to surgery, pain in immediate post-op period, and change in pain after surgery.
RESULTS
Forty-three individuals commented on their TMR experience. Among them, 31 had favorable surgical outcomes, 7 felt that the surgery worsened their pain or there was no significant change in their pain levels, and 5 commented during the initial post-operative period. Twenty-four patients described their pain in the immediate post-operative period and all patients said that the post-operative pain was worse than chronic pain. Among the 28 authors who commented on overall reduction in chronic pain, 24 reported that TMR reduced their pain, whereas 4 reported no change or worsened pain.
CONCLUSIONS
The number of patients (24) who reported improvement in chronic pain aligns with the results in current literature suggesting that TMR is a viable treatment option for pain management. With the current medical management of similar conditions, up to 80% of patients remain unsatisfied with pain management. This analysis supports the evidence that TMR is an effective treatment for patients experiencing post-amputation pain.
Topics: Humans; Social Media; Chronic Pain; Nerve Transfer; Muscle, Skeletal; Pain, Postoperative
PubMed: 38428231
DOI: 10.1016/j.bjps.2024.02.051 -
Revista Espanola de Salud Publica Feb 2024Amputations in work accidents are a phenomenon with a high incidence and peculiar characteristics. The few studies about the effects of amputation are referred to large... (Review)
Review
OBJECTIVE
Amputations in work accidents are a phenomenon with a high incidence and peculiar characteristics. The few studies about the effects of amputation are referred to large limbs, and show that, beyond the physical consequences, there are important psychological consequences. The goal of this paper was to show the updated knowledge on the main psychopathological consequences of amputations in work accidents, as well as the variables that can modulate them.
METHODS
A non-systematic bibliographic review was carried out, with varied ad hoc searches for the different variables studied.
RESULTS
Studies have focused mainly on anxiety and depressive symptoms, post-traumatic stress disorder, and phantom limb pain. Modulating variables whose presence improves the prognosis of these persons have been identified, such as adaptation to daily life, physical exercise, coping strategies, resilience and quality of life.
CONCLUSIONS
The different psychological areas reviewed should be considered when attending people who have suffered an amputation in a work accident. Likewise, enhancing the modulating variables whose presence improves the prognosis is an interesting field for professional intervention.
Topics: Humans; Quality of Life; Spain; Amputation, Surgical; Anxiety; Accidents
PubMed: 38421014
DOI: No ID Found -
Handchirurgie, Mikrochirurgie,... Feb 2024The upper extremity and particularly the hands are crucial for patients in interacting with their environment, therefore amputations or severe damage with loss of hand...
BACKGROUND
The upper extremity and particularly the hands are crucial for patients in interacting with their environment, therefore amputations or severe damage with loss of hand function significantly impact their quality of life. In cases where biological reconstruction is not feasible or does not lead to sufficient success, bionic reconstruction plays a key role in patient care. Classical myoelectric prostheses are controlled using two signals derived from surface electrodes in the area of the stump muscles. Prosthesis control, especially in high amputations, is then limited and cumbersome. The surgical technique of Targeted Muscle Reinnervation (TMR) offers an innovative solution: The major arm nerves that have lost their target organs due to amputation are rerouted to muscles in the stump area. This enables the establishment of cognitive control signals that allow significantly improved prosthesis control.
PATIENTS/MATERIALS AND METHODS
A selective literature review on TMR and bionic reconstruction was conducted, incorporating relevant articles and discussing them considering the clinical experience of our research group. Additionally, a clinical case is presented.
RESULTS
Bionic reconstruction combined with Targeted Muscle Reinnervation enables intuitive prosthetic control with simultaneous movement of various prosthetic degrees of freedom and the treatment of neuroma and phantom limb pain. Long-term success requires a high level of patient compliance and intensive signal training during the prosthetic rehabilitation phase. Despite technological advances, challenges persist, especially in enhancing signal transmission and integrating natural sensory feedback into bionic prostheses.
CONCLUSION
TMR surgery represents a significant advancement in the bionic care of amputees. Employing selective nerve transfers for signal multiplication and amplification, opens up possibilities for improving myoelectric prosthesis function and thus enhancing patient care. Advances in the area of external prosthetic components, improvements in the skeletal connection due to osseointegration and more fluid signal transmission using wireless, fully implanted electrode systems will lead to significant progress in bionic reconstruction, both in terms of precision of movement and embodiment.
Topics: Humans; Quality of Life; Amputation, Surgical; Upper Extremity; Amputation Stumps; Prosthesis Implantation; Artificial Limbs; Muscle, Skeletal
PubMed: 38417811
DOI: 10.1055/a-2260-9842 -
Regional Anesthesia and Pain Medicine Feb 2024Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often... (Review)
Review
BACKGROUND
Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear.
OBJECTIVE
The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP.
EVIDENCE REVIEW
We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events.
FINDINGS
The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low).
CONCLUSIONS
The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs.
PROSPERO REGISTRATION NUMBER
CRD42023455949.
PubMed: 38388020
DOI: 10.1136/rapm-2023-105104 -
Neurophysiologie Clinique = Clinical... Feb 2024Phantom pain limb (PLP) has gained more attention due to the large number of people with amputations around the world and growing knowledge of the pain process, although...
BACKGROUND
Phantom pain limb (PLP) has gained more attention due to the large number of people with amputations around the world and growing knowledge of the pain process, although its mechanisms are not completely understood.
OBJECTIVES
The aim of this study was to understand, in patients with amputations, the association between PLP and residual limb pain (RLP), and the brain metabolic response in cortical motor circuits, using functional near-infrared spectroscopy (fNIRS).
METHODS
Sixty participants were recruited from the rehabilitation program in São Paulo, Brazil. Included patients were aged over 18 years, with traumatic unilateral lower-limb amputation, with PLP for at least 3 months after full recovery from amputation surgery. PLP and RLP levels were measured using visual analogue scales. fNIRS was performed during motor execution and motor mirror tasks for 20 s. In order to highlight possible variables related to variation in pain measures, univariate linear regression analyses were performed for both experimental conditions, resulting in four fNIRS variables (two hemispheres x two experimental conditions). Later, in order to test the topographic specificity of the models, eight multivariate regression analyses were performed (two pain scales x two experimental conditions x two hemispheres), including the primary motor cortex (PMC) related channel as an independent variable as well as five other channels related to the premotor area, supplementary area, and somatosensory cortex. All models were controlled for age, sex, ethnicity, and education.
RESULTS
We found that: i) there is an asymmetric metabolic activation during motor execution and mirror task between hemispheres (with a predominance that is ipsilateral to the amputated limb), ii) increased metabolic response in the PMC ipsilateral to the amputation is associated with increased PLP (during both experimental tasks), while increased metabolic response in the contralateral PMC is associated with increased RLP (during the mirror motor task only); ii) increased metabolic activity of the ipsilateral premotor region is associated with increased PLP during the motor mirror task; iii) RLP was only associated with higher metabolic activity in the contralateral PMC and lower metabolic activity in the ipsilateral inferior frontal region during motor mirror task, but PLP was associated with higher metabolic activity during both tasks.
CONCLUSION
These results suggest there is both task and region specificity for the association between the brain metabolic response and the two different types of post-amputation pain. The metabolic predominance that is ipsilateral to the amputated limb during both tasks was associated with higher levels of PLP, suggesting a cortical motor network activity imbalance due to potential interhemispheric compensatory mechanisms. The present work contributes to the understanding of the underlying topographical patterns in the motor-related circuits associated with pain after amputations.
Topics: Humans; Adult; Middle Aged; Motor Cortex; Spectroscopy, Near-Infrared; Brazil; Amputation, Surgical; Phantom Limb; Lower Extremity
PubMed: 38382136
DOI: 10.1016/j.neucli.2023.102939 -
Current Pain and Headache Reports May 2024The purpose of this review is to evaluate and summarize the literature investigating cryoneurolysis in the treatment of various chronic pain pathologies. (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to evaluate and summarize the literature investigating cryoneurolysis in the treatment of various chronic pain pathologies.
RECENT FINDINGS
There is an increasing amount of interest in the use of cryoneurolysis in chronic pain, and various studies have investigated its use in lumbar facet joint pain, SI joint pain, post-thoracotomy syndrome, temporomandibular joint pain, chronic knee pain, phantom limb pain, neuropathic pain, and abdominal pain. Numerous retrospective studies and a more limited number of prospective, sham-controlled prospective studies suggest the efficacy of cryoneurolysis in managing these chronic pain pathologies with a low complication rate. However, more blinded, controlled, prospective studies comparing cryoneurolysis to other techniques are needed to clarify its relative risks and advantages.
Topics: Humans; Chronic Pain; Cryosurgery; Cryotherapy; Pain Management
PubMed: 38372950
DOI: 10.1007/s11916-024-01222-w