Association of Peripheral Serum MicroRNAs With Persistent Phantom Limb Pain in Individuals With Amputation.

OBJECTIVE: Individuals with major limb amputation(s) frequently experience phantom limb sensations, which are described as vivid impressions of either parts or entire missing limb(s). Despite the high incidence and prevalence of phantom limb pain, the underlying pathophysiology of phantom limb pain remains poorly understood. The objective of this study was to evaluate a possible role of microRNAs in the pathophysiology of phantom limb pain. DESIGN: Adults with acquired limb amputation and varying degrees of phantom limb pain consented to provide clinical data and blood samples. One hundred forty participants with single or multiple limb amputation(s) were enrolled. The Visual analog scale and neuropathic pain symptom inventory were administered to evaluate the pain. Serum samples were analyzed for microRNA expression and bioinformatic analysis was performed. RESULTS: Sixty-seven participants did not experience phantom limb pain, whereas 73 participants experienced varying severities of phantom limb pain measured on a pain scale. Linear regression analysis suggested that the time since amputation is inversely related to severity of the pain. A significantly increased expression of 16 microRNAs was observed in participants experiencing phantom limb pain. Bioinformatic analysis shows a possible role of these microRNAs in regulating genes expressed in peripheral neuropathy. CONCLUSIONS: This study provides the first evidence of association of microRNA in phantom limb pain.

Characteristics of phantom limb pain in U.S. civilians and service members.

OBJECTIVES: The population of Americans with limb loss is on the rise, with a different profile than in previous generations (e.g., greater incidence of amputation due to diabetes). This study aimed to identify the key characteristics of phantom limb sensation (PLS) and pain (PLP) in a current sample of Americans with limb loss. METHODS: This cross-sectional study is the first large-scale (n=649) study on PLP in the current population of Americans with limb loss. A convenience sample of military and civilian persons missing one or more major limbs was surveyed regarding their health history and experience with phantom limb phenomena. RESULTS: Of the participants surveyed, 87% experienced PLS and 82% experienced PLP. PLS and PLP typically first occurred immediately after amputation (47% of cases), but for a small percentage (3-4%) onset did not occur until over a year after amputation. Recent PLP severity decreased over time (ß=0.028, 95% CI: -0.05-0.11), but most participants reported PLP even 10 years after amputation. Higher levels of recent PLP were associated with telescoping (ß=0.123, 95% CI: 0.04-0.21) and higher levels of pre-amputation pain (ß=0.104, 95% CI: 0.03-0.18). Those with congenitally missing limbs experienced lower levels of recent PLP (t (37.93)=3.93, p<0.01) but there were no consistent differences in PLP between other amputation etiologies. CONCLUSIONS: Phantom limb phenomena are common and enduring. Telescoping and pre-amputation pain are associated with higher PLP. Persons with congenitally missing limbs experience lower levels of PLP than those with amputation(s), yet PLP is common even in this subpopulation.

What Sexual and Gender Minority People Want Researchers to Know About Sexual Orientation and Gender Identity Questions: A Qualitative Study.

Sexual and gender minority (SGM) people-including members of the lesbian, gay, bisexual, transgender, and queer communities-are understudied and underrepresented in research. Current sexual orientation and gender identity (SOGI) questions do not sufficiently engage SGM people, and there is a critical gap in understanding how SOGI questions reduce inclusion and accurate empirical representation. We conducted a qualitative study to answer the question, "For SGM people, what are the major limitations with current SOGI questions?" Focus groups probed reactions to SOGI questions adapted from prior national surveys and clinical best practice guidelines. Questions were refined and presented in semi-structured cognitive interviews. Template analysis using a priori themes guided analysis. There were 74 participants: 55 in nine focus groups and 19 in cognitive interviews. Participants were diverse: 51.3% identified as gender minorities, 87.8% as sexual minorities, 8.1% as Hispanic/Latinx, 13.5% as Black or African-American, and 43.2% as Non-white. Two major themes emerged: (1) SOGI questions did not allow for identity fluidity and complexity, reducing inclusion and representation, and (2) SOGI question stems and answer choices were often not clear as to which SOGI dimension was being assessed. To our knowledge, this represents the largest body of qualitative data studying SGM perspectives when responding to SOGI questions. We present recommendations for future development and use of SOGI measures. Attention to these topics may improve meaningful participation of SGM people in research and implementation of such research within and for SGM communities.

Trajectory of phantom limb pain relief using mirror therapy: Retrospective analysis of two studies.

BACKGROUND AND PURPOSE: Research indicates that mirror therapy reduces phantom limb pain (PLP). Objectives were to determine when mirror therapy works in those who respond to treatment, the relevance of baseline PLP to when pain relief occurs, and what pain symptoms respond to mirror therapy. METHODS: Data from two independent cohorts with unilateral lower limb amputation were analyzed for this study (n=33). Mirror therapy consisted of 15-min sessions in which amputees performed synchronous movements of the phantom and intact legs/feet. PLP was measured using a visual analogue scale and the Short-Form McGill Pain Questionnaire. RESULTS: The severity of PLP at the beginning of treatment predicted when pain relief occurred. Those with low baseline PLP experienced a reduction (p<0.05) in PLP by session 7 of treatment, those with medium baseline PLP experienced pain relief by session 14 of treatment, and those with high baseline PLP experienced pain relief by session 21 of treatment. Mirror therapy reduced throbbing, shooting, stabbing, sharp, cramping, aching, tender, splitting, tiring/exhausting, and punishing-cruel pain symptoms. CONCLUSION: The degree of PLP at baseline predicts when mirror therapy relieves pain. IMPLICATIONS: This article indicates that the degree of baseline PLP affects when mirror therapy relieves pain: relief occurs by session 7 in patients with low PLP but by session 21 in patients with high PLP. Clinicians should anticipate slower pain relief in patients who begin treatment with high levels of pain. ClinicalTrials.gov numbers:NCT00623818 and NCT00662415.

A Randomized, Controlled Trial of Mirror Therapy for Upper Extremity Phantom Limb Pain in Male Amputees.

OBJECTIVE: Phantom limb pain (PLP) is prevalent in patients post-amputation and is difficult to treat. We assessed the efficacy of mirror therapy in relieving PLP in unilateral, upper extremity male amputees. METHODS: Fifteen participants from Walter Reed and Brooke Army Medical Centers were randomly assigned to one of two groups: mirror therapy (n = 9) or control (n = 6, covered mirror or mental visualization therapy). Participants were asked to perform 15 min of their assigned therapy daily for 5 days/week for 4 weeks. The primary outcome was pain as measured using a 100-mm Visual Analog Scale. RESULTS: Subjects in the mirror therapy group had a significant decrease in pain scores, from a mean of 44.1 (SD = 17.0) to 27.5 (SD = 17.2) mm (p = 0.002). In addition, there was a significant decrease in daily time experiencing pain, from a mean of 1,022 (SD = 673) to 448 (SD = 565) minutes (p = 0.003). By contrast, the control group had neither diminished pain (p = 0.65) nor decreased overall time experiencing pain (p = 0.49). A pain decrement response seen by the 10th treatment session was predictive of final efficacy. CONCLUSION: These results confirm that mirror therapy is an effective therapy for PLP in unilateral, upper extremity male amputees, reducing both severity and duration of daily episodes. REGISTRATION: NCT0030144 ClinicalTrials.gov.

Reversal of phantom pain and hand-to-face remapping after brachial plexus avulsion.

Following left brachial plexus avulsion, a 20-year-old man had phantom limb pain and remapping of sensation from his paralyzed hand onto his face. Mirror therapy (15 min daily, 5 days/week) led immediately to good movement of the phantom limb with decreased pain. Within 2 weeks following nerve graft surgery, remapping of hand sensation onto the face disappeared along with resolution of phantom limb pain. Mirror therapy coupled with nerve grafting may relieve phantom limb pain due to brachial plexus avulsion and reverse hand-to-face remapping, suggesting that both peripheral and central mechanisms mediate development of phantom limb pain and cortical reorganization/neuroplasticity after brachial plexus avulsion.

Residual Limb Hyperhidrosis and RimabotulinumtoxinB: A Randomized Placebo-Controlled Study.

OBJECTIVE: To investigate the use of rimabotulinumtoxinB (BoNT/B [Myobloc]) compared with placebo in treating hyperhidrosis in the residual limbs of individuals with amputation. DESIGN: Randomized, double-blind, placebo-controlled pilot study. SETTING: Military medical center. PARTICIPANTS: Male participants (N=9) with 11 major amputations of the lower limbs and who complained of excessive sweating in their residual limbs were enrolled in the study between September 24, 2008 to October 28, 2011. Participants' lower limbs were randomly assigned to receive injections of either BoNT/B (n=7) or placebo (n=4). INTERVENTION: BoNT/B. MAIN OUTCOME MEASURES: The primary efficacy variable was a minimum of 50% reduction in sweat production 4 weeks after the injection as measured via gravimetric sweat analysis after 10 minutes of physical exertion. Secondary analyses were performed on prosthetic function and pain. RESULTS: All volunteers (100%; 7) in the BoNT/B group achieved a minimum of 50% reduction in sweat production as compared with only 50% (2) in the placebo group. The percent reduction was significantly greater for the BoNT/B group than for the placebo group (-72.7%±15.7% vs -32.7%±39.2%; P<.05). Although both groups subjectively self-reported significant sweat reduction and improved prosthetic function (P<.05 for both), objective gravimetric sweat analyses significantly decreased only for the BoNT/B group (2.3±2.3g vs 0.7±1.1g; P<.05). Neither group reported a change in phantom limb pain or residual limb pain (P>.05 for both). CONCLUSIONS: BoNT/B successfully reduces sweat production in individuals with residual limb hyperhidrosis, but does not affect pain. No differences were found in perceived effect on prosthetic use between BoNT/B and placebo groups.