Post-traumatic Neuropathic Pain Research Articles

Mirogabalin as a Therapeutic Option for Neuropathic Pain Emerging Post-endodontic Treatment: A Two-Case Report

IntroductionOcclusal and percussion pain may manifest occasionally following endodontic treatment, influencing retreatment decisions. Two cases of periapical neuropathic pain, classified as post-traumatic trigeminal neuropathic pain according to the International Classification of Orofacial Pain, are presented. Although mirogabalin is effective in managing neuropathic pain, there is a lack of clinical reports on its use for occasional post-traumatic trigeminal neuropathic pain after endodontic treatment. These cases highlight clinical symptoms and successful treatment with mirogabalin for post-traumatic trigeminal neuropathic pain after endodontic treatment, providing clinicians a “take-away” lesson for improving patient condition. MethodsThe patients, referred by their primary dentist due to postendodontic abnormal pain, found no relief with antibiotics or nonsteroidal anti-inflammatory drugs. Although no findings including swelling or periapical radiolucency were observed around the tooth, they experienced occlusal and percussion pain. Local anesthetic testing showed that the pain originated from the peripheral area around the tooth rather than from central sensitization. Dental radiography and cone-beam computed tomography revealed no abnormal findings. Root canal retreatment was performed by a specialist in endodontic treatment. Although endodontic retreatment drastically decreased visual analog scale pain score, pain persisted. Based on the International Classification of Orofacial Pain criteria, diseases other than post-traumatic trigeminal neuropathic pain were excluded. Mirogabalin (10 mg/d) was prescribed once daily before bedtime. ResultsVisual analog scale scores gradually and drastically decreased 2 weeks after mirogabalin therapy. Several months later, no recurrence of postendodontic pain was observed after tapering off and discontinuing mirogabalin. ConclusionsThese findings suggest the possibility of a new treatment method for post-traumatic trigeminal neuropathic pain after endodontic treatment.

Characteristics and outcomes of peripheral neuropathic pain patients with repeated applications of high-concentration capsaicin cutaneous patch: Results of a retrospective chart review in Germany.

The aim of this study was to evaluate patient characteristics, concomitant analgesic medication, and pain intensity in a real-world setting in Germany, focusing on the repeated application of high-concentration capsaicin patch (HCCP) for neuropathic pain. Data were collected from electronic medical records of patients who received at least two HCCP treatments between January 2011 and July 2022. Subgroup analyses were performed based on the number of HCCP treatments, age groups, and specific neuropathic pain conditions. The study was conducted at an outpatient pain center in Wiesbaden, Germany. The study included 97 patients, primarily diagnosed with neuropathic back pain, postoperative or post-traumatic neuropathic pain, and postherpetic neuralgia. The daily dose of concomitant medications (eg, opioids and anticonvulsants) at the start of capsaicin therapy was compared with the average within 2 years of capsaicin therapy. The last observation carried forward method was used if HCCP treatment was discontinued before the end of the 2-year period. The majority of patients received concomitant medications, with opioids, anticonvulsants, and antidepressants being the most common. The average daily morphine equivalent dose decreased significantly during HCCP treatment. Pain intensity at baseline was generally high, but substantial improvements were observed in patients who received at least three HCCP applications. This study provides evidence for the effectiveness of HCCP treatment in reducing pain intensity and concomitant opioid use in patients with neuropathic pain. Further research is needed to explore the long-term outcomes and optimal treatment regimens for different patient populations.

Letter to the Editor Regarding “Dorsal Root Entry Zone Lesioning Following Unresponsive Spinal Cord Stimulation for Post-Traumatic Neuropathic Pain”

Letter to the Editor Regarding “Dorsal Root Entry Zone Lesioning Following Unresponsive Spinal Cord Stimulation for Post-Traumatic Neuropathic Pain”

Regenerative Peripheral Nerve Interface Surgery for the Management of Chronic Posttraumatic Neuropathic Pain.

Chronic pain resulting from peripheral nerve injury remains a common issue in the United States and affects 7 to 10% of the population. Regenerative Peripheral Nerve Interface (RPNI) surgery is an innovative surgical procedure designed to treat posttraumatic neuropathic pain, particularly when a symptomatic neuroma is present on clinical exam. RPNI surgery involves implantation of a transected peripheral nerve into an autologous free muscle graft to provide denervated targets to regenerating axons. RPNI surgery has been found in animal and human studies to be highly effective in addressing postamputation pain. While most studies have reported its uses in the amputation patient population for the treatment of neuroma and phantom limb pain, RPNI surgery has recently been used to address refractory headache, postmastectomy pain, and painful donor sites from the harvest of neurotized flaps. This review summarizes the current understanding of RPNI surgery for the treatment of chronic neuropathic pain.

Onabotulinum toxin a treatment for posttraumatic trigeminal neuropathic pain: case series and literature review

This case series aimed to assess the treatment outcomes of onabotulinum toxin A (BTX-A) in patients with refractory posttraumatic trigeminal neuropathic pain (PTNP) and to conduct a narrative review of the evidence for BTX-A in PTNP. Thirteen patients were treated with BTX-A infiltrations. Patient demographic and pain characteristics, BTX-A administration, and treatment outcomes were retrospectively analyzed. Papers retrieved after a literature search of articles on PTNP treatment using BTX-A were reviewed. Six patients reported an improvement in pain 3 months after the initial BTX-A injection, with 4 patients reporting a 50% reduction. Two patients achieved an 80% reduction in pain score over 3 years of BTX-A therapy. Three patients reported temporary ipsilateral facial muscle weakness. The literature review revealed five case reports on the use of BTX-A in PTNP patients that reported similar effectiveness to the present cohort study. BTX-A may be a potential treatment modality for refractory PTNP, thus reducing the need for polypharmacy. Multiple intraoral BTX-A injections administered over the painful sites are well tolerated, safe and easily practiced. High-quality studies are required to evaluate the long-term therapeutic efficacy and side effects of BTX-A therapy.

Specificities of orofacial neuropathic pain

Head pain and notably orofacial pain differs from spinal pain on pathophysiological, clinical, therapeutic and prognostic levels. Its high prevalence, important impact on quality of life and significant socio-economical burden justify specific study of such type of pain. Among them, neuropathic orofacial pain resulting from disease or trauma of the trigeminal nervous system is among the most difficult types of pain to diagnose and to treat. Deciphering of underlying peripheral and central mechanisms has allowed numerous conceptual, clinical and therapeutic advances, notably the role of neural and non neural cell types, such as glia, immunocytes, vascular endothelial cells or the role of trigeminal sensory complex neural circuitry reconfiguration in the development of post-traumatic trigeminal neuropathic pain. Cellular interactions within the trigeminal ganglion, allowing a better understanding of several painful dental, ocular or cephalalgic comorbidities, are also described.

Does Immediate Long-Span Nerve Allograft Reconstruction Affect the Incidence of Chronic Postsurgical and Neuropathic Pain in the Reconstructed Mandible Following Resection for Benign and Malignant Disease

Peripheral nerve injury can lead to chronic postsurgical pain (CPSP) and neuropathic pain following major surgery. Determine in patients undergoing ablative mandibular operations with transection of the trigeminal nerve: do those who undergo immediate repair, when compared to those whose nerves are not repaired, have a decreased or increased risk for CPSP or post-traumatic trigeminal neuropathic pain (PTTNp)? A multisite, retrospective cohort of patients who underwent resection of the mandible for benign or malignant disease with either no repair or immediate repair of the intentionally transected trigeminal nerve with a long-span nerve allograft were analyzed for the presence or absence of CPSP and PTTNp at 6months. The primary predictor was the immediate repair or no repair of the trigeminal nerve. The primary outcome was the presence or absence of CPSP and PTTNp at 6months postsurgery. There were 13 covariate variables, including age, sex, ethnicity, nerve injury, type of PTTNp, malignant or benign pathology and subtypes of each, use of radiation or chemotherapy, treatment of transected nerve end, longest follow-up time, pain scale, and onset of pain. Two-tailed Student's t test and Welch's t test were performed on mean scores and post hoc logistics and linear regression modeling were performed when indicated. The confidence level for statistical significance was P value <.05. There were 103 and 94 subjects in the immediate and no-repair groups, respectively. The incidence of CPSP in the no-repair group was 22.3% and PTTNp was 2.12%, while there was 3.8% CPSP and 0% PTTNp in the repair group, which was statistically significant (P= <.001). Logistic regression modeling showed a statistically significant inverse relationship between the immediate repair and the incidence of CPSP/PTTNp with an odds ratio of 0.43, 95% confidence interval 0.18 to 1.01, P=.05. Greater age, malignant pathology, and chemo/radiation treatments were covariates found more frequently in the no repair group. Immediate repair of an intentionally transected trigeminal nerve with a long-span nerve allograft during resection of the mandible for both benign and malignant disease appears to reduce CPSP and possibly eliminate the development of PTTNp.

The Use of Microcurrent Therapy in the Treatment of Cases Suffering from Post-Traumatic Trigeminal Neuropathic Pain Secondary to Iatrogenic Dental Treatment

The Use of Microcurrent Therapy in the Treatment of Cases Suffering from Post-Traumatic Trigeminal Neuropathic Pain Secondary to Iatrogenic Dental Treatment

Dorsal Root Entry Zone Lesioning Following Unresponsive Spinal Cord Stimulation for Post-Traumatic Neuropathic Pain

Spinal cord stimulation (SCS) and dorsal root entry zone (DREZ) lesioning are important therapeutic options for intractable post-traumatic neuropathic pain (PNP). However, surgical choice is controversial due to the need to maximize pain relief and reduce complications. This study aims to retrospectively analyze the effect and complications of DREZ lesioning for patients with PNP who were unresponsive to SCS and provide a surgical reference. Demographic data and surgical characteristics of patients with PNP who underwent DREZ lesioning after an unresponsive SCS were reviewed. Long-term outcomes including numeric rating scale, global impression of change, and long-term complications were assessed. Kaplan-Meier analysis was used to evaluate pain-free survival. Of 19 patients with PNP, 8 had brachial plexus injury (BPI), 7 had spinal cord injury, 2 had cauda equina injury, 1 had intercostal nerve injury, and 1 had lumbosacral plexus injury. All patients were unresponsive or had a recurrence of pain after SCS, with an average pain-relief rate of 9.3%. After DREZ lesioning, the mean numeric rating scale scores significantly decreased from 7.6 ± 1.5 to 1.8 ± 1.7, with an average pain-relief rate of 75.3%. Seven patients (36.8%) experienced worsened neurologic dysfunction at the last follow-up. Patients with BPI had a significantly better outcome than other pathologies (P < 0.001) after DREZ lesioning. DREZ lesioning is an effective alternative procedure to SCS for patients with PNP who have lost limb function. Particularly for those with BPI, DREZ lesioning has shown good efficacy and can be considered a preferred surgical option.

Is Presurgical Pain Intensity Related to Postoperative Recurrence of Post-Traumatic Trigeminal Neuropathic Pain?

Post-traumatic trigeminal neuropathic pain (PTTNp) is a challenging condition to treat, and equally as challenging is the identification of surgical outcome variables to guide treatment. The study purpose was to determine if preoperative pain intensity was related to postoperative recurrence of PTTNp. This retrospective cohort study assessed subjects with preoperative PTTNp of either the lingual or inferior alveolar nerves who underwent elective microneurosurgery at a single institution. Two cohorts were established as follows: No PTTNp at 6months (group 1); presence of PTTNp at 6months (group 2). The primary predictor variable was the preoperative visual analog scale (VAS) score. The primary outcome variable was PTTNp (recurrence or no recurrence at 6months). The demographic and injury characteristics of the groups were compared to assess whether they were similar using Wilcoxon rank analysis. Two-tailed Student's t-test was performed to analyze the difference in preoperative mean VAS scores. Multivariate multiple linear regression models were used to determine the association between the covariates on the outcomes of the primary predictor variable and the primary outcome variable. A P value of <.05 was considered statistically significant. Forty-eight patients were included in the final analysis. There were 20 patients with no pain at 6months and 28 with recurrence at 6months following surgery. There was a significant difference in mean preoperative pain intensity between the two groups (P value .04). The mean preoperative VAS score in group 1 was 6.31 (standard deviation, 2.65), while the mean preoperative VAS score in group 2 was 7.75 (standard deviation, 1.95). Regression analysis showed that one covariate, the type of nerve injured, explained some variability of preoperative VAS score, but by only 16% (P value .005). Regression analysis also showed that two covariates, Sunderland classification and time to surgery, explained some of the variability of PTTNp at 6months, by approximately 30% (P value .001). This study showed that presurgical pain intensity level was related to postoperative recurrence in the surgical treatment of PTTNp. In patients with recurrence, the preoperative pain intensity was higher. Other factors, including time interval from injury to surgery, were also related to recurrence.

Pregabalin in Patients with Post-Traumatic Peripheral Neuropathic Pain: A Meta-Analysis of Randomized Controlled Trials.

To investigate the safety and efficacy of pregabalin versus placebo in post-traumatic peripheral neuropathic pain (PTNP). PubMed, Cochrane Library, Web of Science, and Google Scholar were searched for relevant evidence up to January 2022. The Cochran tool was used to assess the quality of randomized clinical trials (RCTs). Data analysis was performed using Comprehensive Meta-Analysis software. Three RCTs involving 821 patients were included in the meta-analysis. A significant difference was observed between pregabalin and placebo in terms of the pain score (the standardized mean difference [SMD] = -0.481, 95% CI: -0.75 to 0.20, P=0.04) and sleep interference (MD= -0.481, 95% CI: -0.75 to 0.20, P=0.00). There was also a significant difference between pregabalin and placebo regarding somnolence (risk ratio [RR] = 2.78; 95% CI: 1.64 to 4.71, P=0.00), dizziness (RR=4.13; 95% CI: 2.71 to 6.28, P=0.00), and disturbance in attention (RR: 2.97; 95% CI: 1.02 to 8.65, P=0.04). However, no significant difference was observed between pregabalin and placebo in terms of headache (RR=1.20; 95% CI: 0.70 to 2.06, P=0.50), fatigue (RR=1.42; 95% CI: 0.82 to 2.47, P=0.20), nausea (RR=1.52; 95% CI: 0.88 to 2.62, P=0.13), constipation (RR=1.84; 95% CI: 0.78 to 4.29, P=0.15), and discontinuation (RR=1.52; 95% CI: 0.45 to 5.06, P=0.49). Compared with placebo, pregabalin showed better efficacy in reducing PTNP and improving sleep interference. However, it was associated with higher adverse events. Further RCTs is needed to confirm these findings.

Successful Management of Unilateral Post-traumatic Neuropathic Mastalgia: A Case Report.

Stellate ganglion block has been described in the management of postmastectomy neuropathic pain. However, its role in the treatment of posttraumatic neuropathic breast pain has not been reported in the literature. We present a case of a 40-year-old female with a chief complaint of severe debilitating pain in her right breast following trauma, refractory to oral medications including conventional analgesics, amitriptyline, pregabalin, and duloxetine. She was successfully managed after administration of ultrasound-guided stellate ganglion block and pulsed radiofrequency ablation of the stellate ganglion. It resulted in significant and prolonged pain relief leading to improved quality of life.

New Perspectives in Peripheral Nerve Surgery for Neuropathic Pain

Background and Aims: Neuropathic pain can occur following intentional or unintentional peripheral nerve injury. The purpose of this review was to determine in patients who have post-traumatic trigeminal neuropathic pain or required ablative mandibular operations with transection of the nerve, do those who undergo immediate or early surgical interventions, when compared to those whose nerves are not repaired or delayed, have a decreased or increased risk for resolving neuropathic pain? Methods: Two single-site and one multi-site retrospective observatory studies of patients who had neuropathic pain prior to operative treatment of the injured nerve and in patients who underwent resection of the mandible for benign or malignant disease with either no repair or immediate repair were analyzed for the presence or absence of neuropathic pain at 6 months post-surgery. The primary predictor variable in the surgical treatment of neuropathic pain pre-existing surgery was the time from injury to repair and the preoperative pain intensity rated by Visual Analogue Scale (VAS). The primary predictor variable in the study of intentional transected nerve was the immediate repair or no repair of the nerve at the time of resection. Results: There was statistically significant difference in the primary outcome based on time from injury to repair. When the time to surgery was less than 200 days, the percentage of patients with no neuropathic pain was greater than 60%. There was a significant difference in mean VAS between those who had no neuropathic pain (6.4,SD 2.68) and those with recurrence (7.75,SD 1.95). Following mandibular resection there was statistically significant difference between the immediate repair and no repair group. Post-hoc logistic regression modeling showed an inverse relationship between the immediate repair and the incidence of chronic postoperative pain and neuropathic pain with an odd ratio &lt;1. Conclusions: In patients with neuropathic pain, earlier diagnosis and treatment, including peripheral nerve surgery, should be considered with the best outcomes when operative interventions occur within 200 days of the injury and pain intensity are mild or moderate on VAS scales. The immediate repair of an intentionally transected trigeminal nerve appears to reduce and possibly eliminate the development of neuropathic and chronic postoperative pain compared to avoiding nerve repair.

Use of 5% lidocaine patch in the management of post-traumatic localized neuropathic pain. Case reports

Use of 5% lidocaine patch in the management of post-traumatic localized neuropathic pain. Case reports

How Does Changing the Time to Surgery Affect the Recurrence of Post-Traumatic Trigeminal Neuropathic Pain

The recurrence of post-traumatic trigeminal neuropathic pain (PTTNp) following peripheral microneurosurgery continues to be poorly understood. The objective of this study was to determine if the time from injury to surgery of the trigeminal nerve in patients with PTTNp affected the recurrence of PTTNp following surgery. A retrospective cohort of patients with PTTNp prior to trigeminal nerve surgery at a single institute was analyzed for the presence or absence of PTTNp at 6months postsurgery. The primary predictor was the time from injury to surgical treatment and the primary outcome was the presence or absence of PTTNp using subjective and objective neurosensory testing at 6months. Four groups were predefined to evaluate the effect of time to surgery: Group 1 (0 to 100days), Group 2 (101 to 200days), Group 3 (201 to 300days), and Group 4 (> 300days). Repeated measures analysis of variance was used to assess differences in the presence or absence of PTTNp among groups. If a statistical difference was found, a post hoc Tukey-Kramer test was performed. Sixty of 63 eligible patients met inclusion and exclusion criteria with end points at 6months. The weighted mean PTTNp score in Group 1 was 1.6±0.32, Group 2 was 1.61±0.18, Group 3 was 1.3±0.29, and Group 4 was 1±0.0. There was a statistically significant difference in the primary outcome among the groups based on time from injury to repair (P=.0002). The between-group differences were significant for Group 1 and 3 and 4 and between Group 2 and 3 and 4 (P<.01). Within the 4 cohorts, the percentage of patients with PTTNp before surgery with no neuropathic pain at the 6-month follow-up was 41.6%. However, between the 4 cohorts, when the time to surgery was 200days or less, the percentage of patients with PTTNp before surgery with no neuropathic pain at the 6-month follow-up was more than 60%. Time from injury to surgery appears to have an effect on the recurrence of PTTNp. Best outcomes are associated with operative interventions within 200days of the injury.

Pathophysiology of Post-Traumatic Trigeminal Neuropathic Pain

Trigeminal nerve injury is one of the causes of chronic orofacial pain. Patients suffering from this condition have a significantly reduced quality of life. The currently available management modalities are associated with limited success. This article reviews some of the common causes and clinical features associated with post-traumatic trigeminal neuropathic pain (PTNP). A cascade of events in the peripheral and central nervous system function is involved in the pathophysiology of pain following nerve injuries. Central and peripheral processes occur in tandem and may often be co-dependent. Due to the complexity of central mechanisms, only peripheral events contributing to the pathophysiology have been reviewed in this article. Future investigations will hopefully help gain insight into trigeminal-specific events in the pathophysiology of the development and maintenance of neuropathic pain secondary to nerve injury and enable the development of new therapeutic modalities.

Presurgical Pain Intensity is Related to Outcome Following Surgical Treatment of Post-Traumatic Trigeminal Neuropathic Pain

Presurgical Pain Intensity is Related to Outcome Following Surgical Treatment of Post-Traumatic Trigeminal Neuropathic Pain

Gesichtsschmerzerkrankungen mit Relevanz für die Mund‑, Kiefer- und Gesichtschirurgie

Orofacial pain plays a significant role in oral and maxillofacial surgery diagnostics. Patients suffering from orofacial pain present symptoms that are often initially difficult to classify because of the lack of a dental correlate as a physical focus. The International Classification of Orofacial Pain provides an overview of orofacial pain disorders. Relevant representatives include trigeminal neuralgia and orofacial pain resembling the presentation of primary headache disorders such as facial migraine. Furthermore, posttraumatic neuropathic trigeminal pain and idiopathic orofacial pain are described. For these disorders, a strictly conservative approach with involvement of neurologic outpatient clinics specializing in orofacial pain, early pain psychology referral, and attunement to a long treatment duration is recommended.

Post-traumatic Trigeminal Neuropathic Pain: Factors Affecting Surgical Treatment Outcomes.

Post-traumatic trigeminal neuropathic pain (PTTNp) is a painful condition that may result from injury to the sensory division of the trigeminal nerve. Treatment of this condition is challenging and consensus on treatment to resolve neuropathic pain has yet to be standardized. Equally as challenging is the identification of surgical outcome variables to guide surgical treatment of PTTNp. This is partly due to the variability in pain characteristics, severity of nerve injury, location, and duration from injury to surgery. In those with neuropathic pain prior to microsurgical intervention, the incidence of neuropathic pain after microsurgical intervention is 67%. It is unclear why nerve repair surgery is effective in resolving or decreasing neuropathic pain in some patients, whereas it has no effect on pain relief in others. Psychological, medical, and age-related factors have been identified as risk factors for developing chronic post-surgical pain due to post-traumatic neuropathic pain. Two factors: injury to surgery time and preoperative visual analog scale score have recently been identified as variables that influence surgical outcomes in the treatment of PTTNp.

Prevalence of post-traumatic neuropathic pain after digital nerve repair and finger amputation

Post-traumatic neuropathic pain is a major factor affecting the quality of life after finger trauma and is reported with considerable variance in the literature. This can partially be attributed to the different methods of determining neuropathic pain. The Douleur Neuropathique 4 (DN4) has been validated to be a reliable and non-invasive tool to assess the presence of neuropathic pain. This study investigated the prevalence of neuropathic pain after finger amputation or digital nerve repair using the DN4 questionnaire. Patients with finger amputation or digital nerve repair were identified between 2011 and 2018 at our institution. After a minimal follow-up of 12 months, the short form DN4 (S-DN4) was used to assess neuropathic pain. A total of 120 patients were included: 50 patients with 91 digital amputations and 70 patients with 87 fingers with digital nerve repair. In the amputation group, 32% of the patients had pain, and 18% had neuropathic pain. In the digital nerve repair group, 38% of the patients had pain, and 14% had neuropathic pain. Secondly, of patient-, trauma-, and treatment-specific factors, only the time between trauma and surgery had a significant negative influence on the prevalence of neuropathic pain in patients with digital nerve repair. This study shows that persistent pain and neuropathic pain are common after finger trauma with nerve damage. One of the significant prognostic factors in developing neuropathic pain is treatment delay between trauma and time of digital nerve repair, which is of major clinical relevance for surgical planning of these injuries.