Treatment Of Phantom Limb Pain Research Articles

Curative and preemptive treatment of amputee pain by targeted muscle reinnervation: experience from a French military trauma center.

Targeted muscle reinnervation (TMR) is a technique that has proven effective for the treatment and prevention of chronic pain following amputation, though its adoption remains limited. The authors report on their initial experience using TMR. A prospective study was conducted in a military trauma center involving traumatic amputees treated with either curative or preemptive TMR. Their outcomes were compared to those of control patients who underwent neuroma burial or simple neurectomy during primary amputation. Data included a numerical rating scale (NRS) and patient-reported outcomes measurement information System (PROMIS) scores evaluating residual limb pain (RLP) and phantom limb pain (PLP). Eighteen patients with a median age of 45.5 years were included and followed up for a median period of 13 months. The curative TMR group consisted of 8 patients whose results were compared to those of 9 control patients. There was a significant reduction in almost all pain scores with TMR and only in RPL NRS scores with neuroma burial. Reduction in RLP and PLP scores was significantly greater with TMR. The preemptive TMR group included 10 patients whose results were compared to those of 18 control patients. No significant difference was observed in the postoperative evolution of RLP or PLP. These results confirm the benefits of TMR for the curative treatment of RLP and PLP. However, within the limits of this small sample size, preemptive TMR did not show added value. TMR appears to be a complex technique that requires a learning curve.

Examining heterogeneity and reporting of mirror therapy intervention for phantom limb pain: A scoping review.

Mirror therapy shows promise in the treatment of phantom limb pain but lacks robust evidence. To address this gap, we conducted a scoping review aiming to comprehensively explore the landscape of mirror therapy practice, gather details about the session content, and offer recommendations for future research. We searched seven databases for published work from 1995 to May 2023. Two independent reviewers selected, assessed, and extracted data from eligible articles. Articles, regardless of study design, were considered eligible if they investigated mirror therapy as an intervention for phantom limb pain. A total of 44 articles were included, comprising 16 randomized control trials, 14 prospective cohort studies, 15 case reports, and 3 protocols. These studies collectively involved 942 patients, with male patients representing 70 % of the participants. Lower limb amputation, primarily attributed to trauma, accounted for 88 % of the included patients. Pain intensity was predominantly assessed by a visual analog scale (61 %). However, there was a notable absence of detailed descriptions regarding mirror therapy sessions, particularly concerning the number of exercises, duration per exercise, and repetitions. Typically, sessions lasted 15 min each, conducted once daily. The exercises primarily focused on motor exercises targeting the distal part of the limb. The practice of mirror therapy was characterized by poor description, showed significant heterogeneity, and a lack of standardized protocols, which contributes to an overall low level of evidence. Addressing these gaps in practice description and standardization is crucial for improving reproducibility and strengthening the evidence base for the prescription of mirror therapy.

Efficacy of peripheral nerve stimulation in refractory postamputation pain: A narrative review.

The management of postamputation pain remains a significant clinical challenge, with existing therapeutic approaches often yielding inconsistent outcomes. Neuromodulation techniques, particularly peripheral nerve stimulation (PNS), have emerged as promising interventions. However, the evidence supporting their effectiveness in treating phantom limb pain (PLP) and residual limb pain (RLP) remains limited. This narrative review consolidates previous findings of PNS as a postamputation agent and amasses the most recent data on its effectiveness in clinical settings. A literature review was conducted using MEDLINE via PubMed, EMBASE, and Cochrane Library, yielding 115 references. After removing duplicates and applying inclusion criteria, three studies were included. The studies reviewed demonstrate that PNS can offer varying degrees of sustained pain relief, mood enhancement, reduction in opioid use, and functional improvement. However, discrepancies in study design, patient demographics, devices used, and methodological approaches significantly limit the generalizability and reliability of these findings. Currently, the evidence supporting PNS for the treatment of RLP and PLP is limited, with minimal data affirming its efficacy in alleviating postamputation pain and related symptoms. More studies, especially larger, well-designed comparative and observational studies are needed to extrapolate these conclusions for PNS and postamputation pain.

Silencing the Phantom - Pregabalin Misuse in Amputation Patients: A Case Report

In the aftermath of amputation, individuals face not only physical pain but also psychological challenges as their body's integrity is suddenly disrupted. Phantom limb sensations, characterized by the feeling that the amputated limb still exists, are common after amputation. Phantom limb pain often accompanies these sensations. Beyond the physiological aspects, patients' psychological adaptation journey is pivotal. This case report delves into the intricate relationship between phantom limb sensations, psychological factors, and pregabalin use disorder in a right-arm amputee patient. A 25-year-old right-arm amputee male patient went to an addiction outpatient clinic for pregabalin addiction treatment. He had a history of cannabis use to cope with his sadness during his adolescence. While cannabis use initially provided emotional relief, it later turned to pregabalin misuse, escalating to alarming doses (3000mg/day). Many pharmacological agents, including pregabalin, are being tried to treat phantom limb pain. Beyond its positive effects in phantom limb pain treatment, many studies have been published about its addictive features recently. This case underscores the need for comprehensive care for amputees, including psychological support, early prosthetic intervention, social reintegration, and judicious medication management. This case report serves as a reminder that the post-amputation period is not just a physical struggle but also a complex psychological journey toward healing and reintegration into a fulfilling life..

Extended reality used in the treatment of phantom limb pain: a multicenter, double-blind, randomized controlled trial

Abstract Phantom limb pain (PLP) represents a significant challenge after amputation. This study investigated the use of phantom motor execution (PME) and phantom motor imagery (PMI) facilitated by extended reality (XR) for the treatment of PLP. Both treatments used XR, but PME involved overt execution of phantom movements, relying on the decoding of motor intent using machine learning to enable real-time control in XR. In contrast, PMI involved mental rehearsal of phantom movements guided by XR. The study hypothesized that PME would be superior to PMI. A multicenter, double-blind, randomized controlled trial was conducted in 9 outpatient clinics across 7 countries. Eighty-one participants with PLP were randomly assigned to PME or PMI training. The primary outcome was the change in PLP, measured by the Pain Rating Index, from baseline to treatment cessation. Secondary outcomes included various aspects related to PLP, such as the rate of clinically meaningful reduction in pain (CMRP; >50% pain decrease). No evidence was found for superiority of overt execution (PME) over imagery (PMI) using XR. PLP decreased by 64.5% and 68.2% in PME and PMI groups, respectively. Thirty-seven PME participants (71%) and 19 PMI participants (68%) experienced CMRP. Positive changes were recorded in all other outcomes, without group differences. Pain reduction for PME was larger than previously reported. Despite our initial hypothesis not being confirmed, PME and PMI, aided by XR, are likely to offer meaningful PLP relief to most patients. These findings merit consideration of these therapies as viable treatment options and alternatives to pharmacological treatments.

Developing transcranial direct current stimulation as a treatment for phantom limb pain: from pilot mechanistic studies to large clinical studies.

Developing transcranial direct current stimulation as a treatment for phantom limb pain: from pilot mechanistic studies to large clinical studies.

Use of Peripheral Nerve Stimulation and Perineural Catheter to Treat Phantom Limb Pain in a Multiple Limb Amputee: Case Report

BACKGROUND: Limb loss is a debilitating condition affecting many Americans and approximately 80% go on to suffer phantom limb pain (PLP). Peripheral nerve stimulation (PNS) and perineural catheter (PC) placement are promising treatment options for PLP. CASE REPORT: We present a 36-year-old man, who underwent right transhumeral and right transtibial amputations following a work-related accident. He developed significant PLP of both limbs. The right upper extremity PLP was treated first during the inpatient hospital course with a 5-day infusion of 0.5% ropivacaine via a PC. The right lower extremity PLP was later addressed in the outpatient setting with a diagnostic right sciatic/saphenous nerve block followed by a 60-day PNS lead placement, which provided > 50% pain relief from baseline. The patient continues to have > 50% pain relief in his RLE nearly 9 months after the initial procedure. CONCLUSIONS: Our case adds to a growing body of evidence that supports the utility of PNS and PC. Future studies should explore whether early intervention with PNS could improve long-term outcomes. In addition, clinicians could consider the use of a PC for intractable PLP as an opioid-sparing strategy in the inpatient setting where close monitoring is feasible. KEY WORDS: Phantom limb pain, traumatic amputation, peripheral nerve stimulation, perineural catheter

Botulinum toxin therapy for management of phantom and residual limb pain following amputation: A systematic review.

Chronic pain following amputation is debilitating. Due to its mechanisms in modulating muscle contraction and pain, botulinum toxin has been investigated as a treatment option for phantom limb pain (PLP) and residual limb pain (RLP). The objective of this study was to determine the efficacy of botulinum toxin injection in the management of PLP and RLP following major limb amputation using a systematic review of the literature. The databases Medline, CINAHL, EMBASE, Scopus, Web of Science, and Cochrane were searched from inception through October 30, 2023. The search identified 50 articles; 37 underwent full-text review, and 11 were included in the final review. Eighty-nine individuals with pain were investigated by the included studies; 53 had RLP and 63 had PLP. There was significant variation in botulinum toxin type, injection method, and dosage. Twenty-one (53.9%) and 27 (64.3%) participants had improvement in PLP and RLP following botulinum toxin injection, respectively. Therefore, there is potential for use of botulinum toxin for the treatment of PLP and RLP. However, due to the minimal number of studies, small sample sizes, and heterogenous methodologies, our ability to conclude with certainty the efficacy of botulinum toxin injection on the treatment of PLP and RLP following amputation is limited.

Application of AR technology in the treatment of Phantom Limb Pain

In recent years, with the continuous occurrence of accidents such as car accidents, wars, engineering accidents, natural disasters, tumors and vascular diseases, the number of patients with limb disability due to amputations or accidental injuries is also increasing. phantom limb pain (PLP), one of the main complications after amputation, has attracted increasing attention. Phantom limb pain, also known as phantom limb pain, refers to the subjective feeling that the amputated limb still exists, and is accompanied by varying degrees of pain, and the pain is mostly in the distal end of the amputated limb. Most phantom pain is combined with stump pain or phantom sensation. There are as many as 37 treatments for PLP, considering the high frequency of its occurrence and how much it affects patients. They can be broadly categorized as pharmacotherapy, physical therapy, and psychotherapy. Each of these therapies has its own drawbacks, which AR technology is well equipped to make up for.

From Augmented to Virtual Reality in Plastic Surgery: Blazing the Trail to a New Frontier.

Augmented reality (AR) and virtual reality (VR)-termed mixed reality-have shown promise in the care of operative patients. Currently, AR and VR have well-known applications for craniofacial surgery, specifically in preoperative planning. However, the application of AR/VR technology to other reconstructive challenges has not been widely adopted. Thus, the purpose of this investigation is to outline the current applications of AR and VR in the operative setting. The literature pertaining to the use of AR/VR technology in the operative setting was examined. Emphasis was placed on the use of mixed reality technology in surgical subspecialities, including plastic surgery, oral and maxillofacial surgery, colorectal surgery, neurosurgery, otolaryngology, neurosurgery, and orthopaedic surgery. Presently, mixed reality is widely used in the care of patients requiring complex reconstruction of the craniomaxillofacial skeleton for pre- and intraoperative planning. For upper extremity amputees, there is evidence that VR may be efficacious in the treatment of phantom limb pain. Furthermore, VR has untapped potential as a cost-effective tool for microsurgical education and for training residents on techniques in surgical and nonsurgical aesthetic treatment. There is utility for mixed reality in breast reconstruction for preoperative planning, mapping perforators, and decreasing operative time. VR has well- documented applications in the planning of deep inferior epigastric perforator flaps by creating three-dimensional immersive simulations based on a patient's preoperative computed tomography angiogram. The benefits of AR and VR are numerous for both patients and surgeons. VR has been shown to increase surgical precision and decrease operative time. Furthermore, it is effective for patient-specific rehearsal which uses the patient's exact anatomical data to rehearse the procedure before performing it on the actual patient. Taken together, AR/VR technology can improve patient outcomes, decrease operative times, and lower the burden of care on both patients and health care institutions.

Ten-year phantom limb pain with only four sessions of Fu's subcutaneous needling: A case report and systematic review

Phantom limb pain (PLP) is a distressing consequence commonly encountered by individuals who have undergone amputations. The efficacy of treatment options for PLP is limited. In this study, we present a case of a 64-year-old male who suffered from PLP for a duration of 10 years following an above-the-knee amputation. Despite unsuccessful attempts with painkillers and neurotrophic drugs over the course of a decade, the patient sought relief through Fu's Subcutaneous Needling (FSN), an innovative acupuncture therapy that specifically targets the subcutaneous tissue for pain management. Remarkably, the patient experienced a significant reduction in PLP and subsequently decreased his reliance on medication, as well as experiencing improved sleep after undergoing one session of FSN per day for four consecutive days. A follow-up conducted three years later demonstrated positive treatment outcomes. FSN demonstrated a significant influence on PLP, resulting in reduced analgesic requirements and enhanced quality of life. Therefore, FSN may be recommended as an additional treatment option for PLP. In order to gain a comprehensive understanding of the effects of acupuncture on PLP, a systematic review of relevant literature was conducted in PubMed, Embase, Cochrane Library and Web of Science in recent 20 years (from January 1, 2003 to October 16, 2023), using different combinations of the following terms: (phantom acrodynia), (residual limb pain), (phantom limb pain), (acupuncture), (electroacupuncture), (auriculoacupuncture), and (needling). 9 articles with 18 cases including one randomized controlled trial (n = 8) were obtained. This review provided additional evidence supporting the efficacy and safety of needling therapies for PLP. This systematic review offers additional evidence supporting the effectiveness and safety of needling therapies for PLP. However, there were no precedent reports using FSN treatment for PLP. Hence, this case may provide some implications for clinicians in practice.

Efficacy of Mirror Therapy in Patients with Phantom Pain after Amputation of a Lower Limb: A Systematic Literature Review.

Up to 80% of patients after amputation are affected by phantom limb pain. This may be due to various mechanisms of cortical reorganisation. Non-surgical treatment of the neuropathic phantom limb pain involves mirror therapy. Thereby, the use of a mirror should induce the illusion that the extremity has been preserved. This illusion should initiate processes to restore the original organisation of the somatosensory and motor cortex and thus to reduce pain. Evidence of mirror therapy to treat lower extremity phantom limb pain is rare. Therefore, the aim of this systematic review is to qualitatively analyse the efficacy of mirror therapy for treatment of phantom limb pain in adult patients after unilateral amputations of the lower extremity.The databases Medline (PubMed), Physiotherapy Evidence Database (PEDro), Cochrane Library (Central), and OPENGREY were systematically searched until 26th November 2020, followed by continued searches in these databases to provide a review of updated literature. Study selection, data extraction, and risk of bias evaluation (Risk of Bias Tool [RoB]) of included studies were conducted by two reviewers independently. The primary outcome was pain intensity, and secondary outcomes were pain frequency, pain duration, activities of daily life (ADL), and quality of life. The methodology of this review follows the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Cochrane Handbook for Systematic Reviews of Interventions.The search revealed 234 articles. Four articles were included in the analysis. A reduction in pain intensity due to mirror therapy was reported in all studies, however, in only 2 studies there were significant differences between mirror therapy and the comparison after 4 weeks of treatment (p<0.001; p<0.05). This significant difference was maintained after 3 and 6 months follow-up in one of those studies (p<0.001). The outcomes pain frequency, pain duration, and ADL were decreased after 4 and 10 weeks of mirror therapy compared to comparison, but with no statistical significance (p>0.05). After 6 months, there was a significant improvement in the duration of pain and in ADL after mirror therapy compared with the control group (p<0.05). Differences in the results quality of life between the intervention group and comparison were observed in 2 studies.Mirror therapy of high frequency and duration is an effective intervention to reduce phantom limb pain in patients after unilateral lower extremity amputation. The superiority of mirror therapy to other interventions cannot be concluded, as the evidence was of low quality.

Graded motor imagery and its phases for individuals with phantom limb pain following amputation: A scoping review

Objective Three-phase graded motor imagery (limb laterality, explicit motor imagery, and mirror therapy) has been successful in chronic pain populations. However, when applied to phantom limb pain, an amputation-related pain, investigations often use mirror therapy alone. We aimed to explore evidence for graded motor imagery and its phases to treat phantom limb pain. Data Sources A scoping review was conducted following the JBI Manual of Synthesis and Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews. Thirteen databases, registers, and websites were searched. Review Methods Published works on any date prior to the search (August 2023) were included that involved one or more graded motor imagery phases for participants ages 18+ with amputation and phantom limb pain. Extracted data included study characteristics, participant demographics, treatment characteristics, and outcomes. Results Sixty-one works were included representing 19 countries. Most were uncontrolled studies (31%). Many participants were male (75%) and had unilateral amputations (90%) of varying levels, causes, and duration. Most works examined one treatment phase (92%), most often mirror therapy (84%). Few works (3%) reported three-phase intervention. Dosing was inconsistent across studies. The most measured outcome was pain intensity (95%). Conclusion Despite the success of three-phase graded motor imagery in other pain populations, phantom limb pain research focuses on mirror therapy, largely ignoring other phases. Participant demographics varied, making comparisons difficult. Future work should evaluate graded motor imagery effects and indicators of patient success. The represented countries indicate that graded motor imagery phases are implemented internationally, so future work could have a widespread impact.

Modern concepts of treatment of phantom limb pain

Phantom limb pain is a specific entity of neuropathic pain that develops in 30%85% of patients with amputated limbs and leads to considerable worsening of the quality of life. The number of such cases increases during military conflicts. It can be caused by a traumatic amputation due to mine blast injury, peculiarities of provided medical assistance, and the special psychological state of casualties being in extremely stressful situations at the moment of wounding. Phantom limb pain development is accompanied by multiple functional and structural changes at different levels of the peripheral and central nervous systems. As a result, different theories of pathogenesis are proposed. However, at present, no final opinion concerns mechanisms of phantom limb pain development. Although different versions of drug and non-drug therapy have been suggested, none of them turned out to be universal and fully effective. Many medications were found to be linked to phantom limb pain pathogenesis; however, even first-line therapy drugs (non-steroidal anti-inflammatory drugs, tricyclic antidepressants, narcotic analgesics, and anticonvulsants) often fail to provide adequate analgesia. Long-term prescription of narcotic analgesics is at risk of the development of addictive disorders. Surgical interventions have not demonstrated their effectiveness as well. Thus, their use is justified only in the case of ineffective conservative treatment. Poor efficacy of conventional concepts of phantom limb pain treatment led to the use of new means such as botulinum toxin therapy, non-drug methods (psychotherapy, mirror therapy, biological feedback, virtual reality, acupuncture, massage, hypnosis, etc.). Thus, the search for original methods based on the development and introduction of new drug therapy schemes is imperative. A possible solution to this problem is not only creating absolutely new non-opioid analgesics but also using adjuvant therapeutic means in the multimodality schemes of analgesia. The latter promotes neurotransmission in the antinociceptive system and potentiates the effect of traditional analgesics.

Physical Activity for the Treatment of Phantom Limb Pain

Phantom limb pain (PLP) is a complex and multifactorial phenomenon whereby individuals with an amputation feel intermittent pain or discomfort where the limb used to be. Although there is no specific treatment for PLP, research suggests that participation in regular physical activity may reduce PLP symptoms. This study was designed to examine the relationship between PLP and regular physical activity. Nine lower-limb amputees (18 to 80 years) volunteered to participate in this study. Participants were recruited from online support groups and were invited to complete a Qualtrics survey. Questions regarding time since amputation, PLP symptoms, prior treatments and involvement in physical activity were asked. Most volunteers participated in some form of physical activity but noted they were either unsure or did not have a reduction in the duration of their PLP episodes. However, participation in regular physical activity did lead to a reduction in the intensity and frequency of PLP. Combining physical activity with other treatments did not alter the experience of PLP. These results indicate that health care providers (HCPs) should encourage patients with lower-limb amputations to participate in regular physical activity to maintain and promote physical health and as an intervention to reduce the intensity of PLP. Keywords: amputees, phantom limb pain, treatment, physical activity, exercise

The Coevolution of the Understanding and Treatment Modalities for Phantom Limb Pain

Phantom Limb Pain (PLP), an inappropriate sensation in a missing limb, is a post-amputation phenomenon that occurs in up to 80% of amputees. The specific sensations vary from person to person, but some common reported sensations include warmth or coldness, itching, tingling, and electric shock. Some patients also perceive a specific position or movement of the phantom limb. Most amputees experience PLP with varying degrees of intensity, frequency, and duration. About 5-10% of amputees continue to have severe PLP for many years after amputation. As technology and scientific understanding have evolved, phantom limb pain has become better understood over the centuries, from its first mention from Ambroise Pare in the 1600s to the usage of a variety of medication, medical therapy, and surgery options available today. Although the field of medicine does not yet have a curative treatment for PLP, treatment modalities have advanced from the use of wooden pegs to the latest and advanced prosthetics. By summarizing the growing understanding and evolution of treatment modalities for the medical condition from its first mention in the 16th century to the current 21st century, we can begin to appreciate the years of study and collaboration to current knowledge of phantom limb pain.

Physiotherapy: A potential and novel treatment approach for phantom limb pain in post-amputee patients - A systematic review.

To evaluate the efficacy of conventional and novel non-pharmacologic, non-invasive therapeutic interventions in physiotherapy for the treatment of phantom limb pain (PLP) in post-amputee patients. A systematic search for the articles was conducted in multiple electronic databases such as PUBMED, Google Scholar, EMBASE, Cochrane library and Physiotherapy Evidence Database (PEDro), following the PRISMA method and only published articles from the last 12years (2010-2022) evaluating the efficacy of different physiotherapy interventions for the treatment of PLP in post-amputee patients were included. The methodological quality and risk of bias of the articles were assessed and evaluated by two independent reviewers using the PEDro scale, Methodological index for non-randomized studies scale (MINORS), and Cochrane collaboration's assessment tool. A total of 1840 articles were identified, out of which 17 articles (11 RCTs and 6 pilot studies) were ultimately chosen after the full-text screening. After reviewing the articles, evidence identified in RCTs and pilot studies indicates towards significant improvement in reducing the severity of PLP in post-amputee patients by using different physiotherapy interventions. Physiotherapy interventions with advance modalities and exercises can be used to increase the overall effectiveness of the treatment and to reduce the severity of phantom limb pain in post-amputee patients. However, due to the lack of consistent evidence for a given intervention, it becomes even more difficult to reach a majority consensus as to which intervention better assess all the mechanism of PLP thereby alleviating the problem of PLP in post-amputee patients. Therefore, more rigorous randomized controlled trials will be required in the future to reach a conclusion.

Mirror Therapy in Patients with Somatoform Pain Disorders-A Pilot Study.

Patients with chronic pain report reduced quality of life and high symptom burden while often responding insufficiently to treatment options. Mirror therapy has been proven to be effective in treating phantom limb pain and other conditions such as CRPS. This study was designed to investigate the efficacy of mirror therapy in patients with somatoform pain disorders on symptom severity and associated physiological parameters. Fifteen patients with persistent somatoform pain disorder (F45.40) or chronic pain disorder with somatic and psychological factors (F45.41) participated and received four weeks of tablet-based mirror therapy. Symptom severity was measured with established questionnaires, and their thermal detection, pain thresholds, and heart rate variability (HRV) were also assessed. After mirror therapy, pain intensity was reduced (z = -2.878, p = 0.004), and pain thresholds for cold stimuli were also diminished, i.e., the subjects became more sensitive to cold stimuli (z = -2.040, p = 0.041). In addition, a reduction of absolute power in the low-frequency band of HRV (t(13) = 2.536, p = 0.025) was detected. These findings indicate that this intervention may reduce pain intensity and modulate associated physiological parameters. As these results are limited by several factors, e.g., a small sample size and no control group, they should be validated in further studies investigating this novel intervention in these patients.

Pre-operative sciatic nerve block vs postoperative surgeon-placed perineural stump catheter for prevention of phantom limb pain after below-knee amputation.

Pre-operative sciatic nerve block vs postoperative surgeon-placed perineural stump catheter for prevention of phantom limb pain after below-knee amputation.

Evolving techniques for reducing phantom limb pain.

At least two million people in the United States of America live with lost limbs, and the number is expected to double by 2050, although the incidence of amputations is significantly greater in other parts of the world. Within days to weeks of the amputation, up to 90% of these individuals develop neuropathic pain, presenting as phantom limb pain (PLP). The pain level increases significantly within one year and remains chronic and severe for about 10%. Amputation-induced changes are considered to underlie the causation of PLP. Techniques applied to the central nervous system (CNS) and peripheral nervous system (PNS) are designed to reverse amputation-induced changes, thereby reducing/eliminating PLP. The primary treatment for PLP is the administration of pharmacological agents, some of which are considered but provide no more than short-term pain relief. Alternative techniques are also discussed, which provide only short-term pain relief. Changes induced by various cells and the factors they release are required to change neurons and their environment to reduce/eliminate PLP. It is concluded that novel techniques that utilize autologous platelet-rich plasma (PRP) may provide long-term PLP reduction/elimination.