Effective Pain Treatment Research Articles

The Role of VARVIMAX™ In the Treatment of Chronic Inflammation and Pain in Arthritis and Fibromyalgia

Background: Arthritis and fibromyalgia are chronic inflammatory conditions that cause significant pain and discomfort in affected individuals. Current treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are associated with adverse effects and do not always provide adequate relief. Therefore, there is a need for safe and effective treatments for chronic inflammation and pain in arthritis and fibromyalgia.
 Review of the Literature: This review aims to evaluate the safety and efficacy of VARVIMAX™, a dietary supplement derived from a plant extract, for managing chronic pain in arthritis and fibromyalgia. According to the literature, the prevalence of fibromyalgia and arthritis is still high and even these two conditions occur together. VARVIMAX™ is a dietary supplement derived from a plant extract. VARVIMAX™ contains high levels of anthocyanins, such as Astaxanthins have been shown to possess anti-inflammatory and antioxidant properties. The formulation includes amino acids and flavonoids such as choline L-bitartrate, GABA, L-arginine, black pepper (piperine), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), trans-resveratrol 98% (polygonum cuspidatum extract), which all have anti-inflammatory effects and play a significant role in pain management. Studies have shown that these ingredients have been effective in reducing pain, and inflammation, and improving joint function in patients with arthritis, fibromyalgia, and other inflammatory conditions. The most common side effects reported were gastrointestinal symptoms, such as nausea and diarrhea. 
 Conclusion: VARVIMAX™, a dietary supplement derived from a plant extract Ephedra, shows promise as a safe and effective treatment for chronic pain in arthritis and fibromyalgia. It is composed of several anthocyanins, amino acids, and flavonoids that impart it its characteristic anti-inflammatory and antioxidant properties. This results in reducing pain and inflammation, and improving joint function. Further research is needed to establish its long-term safety and efficacy in a wider range of inflammatory conditions.

Pain Catastrophizing as a Mediator Between Pain Self-Efficacy and Disease Severity in Patients with Fibromyalgia

BackgroundFibromyalgia (FM) is characterized by chronic widespread pain, fatigue, sleep disturbances, cognitive impairment, and mood disturbance. Both pain catastrophizing and pain self-efficacy have been found to be mediators of pain treatment effectiveness. However, whether pain catastrophizing mediates the association between pain self-efficacy and FM severity remains unclear. AimTo examine whether pain catastrophizing mediates the association between pain self-efficacy and disease severity in patients with FM. MethodsThis cross-sectional study included the baseline data of 105 people with FM from a randomized controlled trial. Hierarchical linear regression analysis was performed to examine the predictive ability of pain catastrophizing for FM severity. Furthermore, we examined the mediating effect of pain catastrophizing on the association between pain self-efficacy and FM severity. ResultsPain self-efficacy was negatively associated with pain catastrophizing (β = −.4043, p < .001). FM severity was positively associated with pain catastrophizing (β = .8290, p < .001) and negatively associated with pain self-efficacy (β = −.3486, p = .014). Pain self-efficacy had a direct effect on FM severity (β = −.6837, p < .001) and an indirect effect on FM severity through the effect of pain catastrophizing (β = −.3352, 95% CI bootstrapping −.5008 to −.1858). ConclusionPain catastrophizing independently predicts FM severity and mediates the association between pain self-efficacy and FM severity. Pain catastrophizing should be monitored through interventions aimed at improving pain self-efficacy to reduce symptom burden in patients with FM.

Remodeling dental anatomy vs sham therapy for chronic temporomandibular disorders. A placebo-controlled randomized clinical trial

BackgroundEvidence regarding the etiology or effective treatments for chronic orofacial pain, the majority diagnosed as temporomandibular disorder (TMD), is limited. PurposeTo investigate whether occlusal equilibration therapy (ET) and decreasing the (higher) angle of the lateral guidance on the nonworking-side leads to a reduction in chronic TMDs intensity. MethodsIt was conducted a randomized, explanatory, single blind with blinded assessment, placebo-controlled trial with strong protection against bias involving patients with chronic TMDs. Participants were randomly assigned to receive equilibration therapy or sham therapy. ET in this study consisted of minimal invasive occlusal remodeling to obtain balanced occlusion with reduction of the steeper angle of lateral mandibular movement with respect to the Frankfort plane. The primary outcome was a change in the pain intensity score (on a 0–10 point scale, with 0 indicating no pain and 10 the worst possible pain) at month 6. Secondary outcomes include maximum unassisted mouth opening and psychological distress. ResultsA total of 77 participants underwent randomization, 39 of whom received ET and 38 sham therapy. The trial was stopped early for efficacy, according to preestablished rules when 67 participants (n = 34, n = 33, respectively) had completed the analysis. At month 6, the mean unadjusted pain intensity score was 2.1 in the ET and 3.6 in the sham therapy group (adjusted mean difference, −1.54; 95% confidence interval [CI] −0.5 to −2.6; P = 0.004; ANCOVA model). The mean increase in maximum unassisted mouth opening (main secondary outcome) was significantly higher in the real therapy group (adjusted mean difference 3.1 mm, 95% CI 0.5–5.7, p = 0.02). ConclusionET significantly reduced the intensity of facial pain associated with chronic TMDs and increased maximum unassisted mouth opening, as compared with sham therapy, over the course of 6 months. There were no serious adverse events.Funded by the Instituto de Salud Carlos III from the Ministry of Science and Innovation of the Government of Spain and European Regional Development Fund, Grant nº PI11/02507; “una manera de hacer Europa”.

Factors Influencing Participation in Physical Activity, Sports, and Exercise in Children and Adolescents with Spinal Pain or Spinal Conditions: A Systematic Review and Meta-Ethnography.

Physical activity is an effective treatment for paediatric spinal pain. However, participation rates remain low and review evidence is needed to establish why. This review identifies factors influencing participation in sports, exercise, and physical activity in those aged 18 or under with spinal pain or spinal conditions. Trends or differences between discrete sub-populations are identified. A meta-ethnographic review was undertaken. Qualitative papers were identified and appraised using the JBI checklist. Thematic trends were mapped onto the biopsychosocial model and subthemes identified. Uniqueness was calculated and the confidence in the evidence was evaluated using the GRADE-CERQual tool. Data were gathered from nine qualitative papers (384 participants). Three themes were identified: (1) biological: physical challenges and bladder and bowel care; (2) psychological: perceptions of differences to peers, struggle, anger, sadness, adjustment, and acceptance; and (3) sociological: influence of friends, social acceptance, negative attitudes from others, and the influence of their disability on family routine. Sociological factors were most influential on exercise participation alongside related psychological and biological factors. Adolescents over 14 years offered greater critical insight compared to the younger children. Results are best applied to neuromuscular conditions with further robust evidence required in paediatric musculoskeletal spinal pain.

ID: 222688 Functional Ultrasound Imaging Reveals Activation Properties of Clinical Spinal Cord Stimulation Therapy

Spinal cord stimulation (SCS) therapy has long been established as an effective treatment for chronic neuropathic pain. However, methodological limitations have prohibited the detailed investigation of the activation patterns produced in the spinal cord during therapy. Functional ultrasound (fUS) is an emerging technology that monitors local hemodynamic changes in the brain that are tightly coupled to neural activity1-3. Previous studies have demonstrated that the high spatiotemporal resolution of fUS can be used to monitor activation in the spinal cord during SCS4,5. In this study, fUS was used to investigate neuromodulation patterns produced by clinical SCS paradigms in an ovine model that enabled testing with implanted clinical hardware.

Is transcutaneous electrical nerve stimulation an effective treatment for low back pain?

Eisenhower Army Medical Center, Fort Gordon, GA The corresponding author is Jason Lanham; [email protected] The authors have no conflicts of interest to disclose. The opinions and assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the U.S. Army Medical Department, the Army at large, or the Department of Defense.

Bibliometric Analysis of Research Trends on Tuina Manipulation for Neck Pain Treatment Over the Past 10 Years.

Tuina is an effective treatment for neck pain (NP). However, there has been no bibliometric analysis of the global application and emerging trends of tuina performed for NP. Therefore, this study aimed to provide an overview of the current state and future trends in the field. Articles about tuina for NP, published from January 1, 2013, to January 1, 2023, were searched in the Web of Science Core Collection database. CiteSpace (6.1.R6) and VOSviewer (1.6.18) software were used to analyze annual trends in literature posts, countries, institutions, authors, cited references, and knowledge graphs of keyword co-occurrence, clustering, and burst using standard bibliometric indicators. The final analysis comprised 505 valid documents. The results demonstrate that the number of articles in the field of tuina therapy for NP has gradually increased over the years, showing the most active countries, institutions, journals, and authors. There were 323 keywords in the field, 322 research authors, and 292 research institutions, with the USA having the most publications (n = 140). The most published institution is Vrije University Amsterdam, and the most published journal is the Cochrane Database of Systematic Reviews. Peter R Blanpied is the most influential and most-cited author. Interventions (dry needling, massage therapy, and muscle energy techniques), common treatment sites for NP (upper trapezius), and complications (cervicogenic headache) are the top three frontiers mentioned in the field of tuina research for NP. The bibliometric study showed the current status and trends in clinical research on treating patients with NP using tuina, which may help researchers identify topics of interest and scope for future research in this field.

ID: 210977 Human Perception of Sensing Evoked Compound Action Potential During Spinal Cord Stimulation

Spinal cord stimulation (SCS) is an effective chronic pain treatment, which relies on programming based on patients’ perception of stimulation. Stimulation efficacy changes as the spinal cord moves. Therefore, sensing evoked compound action potential (ECAP) and adjusting stimulation based on ECAP may provide a way to maintain therapy effectiveness [1,2,3,4]. Here, we quantify the ECAP response-dose curves with patients’ perception to understand how to utilize ECAP during potential stimulation adjustment.

ID: 223284 An Objective Analysis of Functional Changes With Spinal Cord Stimulation (SCS)

Introduction: Spinal cord stimulation is an effective treatment for pain of the trunk and extremities as supported by several decades of experience and multiple studies. The current “gold-standard” to indicate therapeutic benefit and enable insurance coverage is achieving at least a 50% reduction in pain during the trial. Some centers choose 5-7day trials and in others extended trials are required to confirm benefit. In addition, previous patient reports suggest a reduction in efficacy over time and the development of “tolerance”. Accumulating evidence suggests a significant relationship between pain level and functional performance.

Case Report: Lower Extremity Paresthesia and Pain with Diabetic Polyneuropathy Combated with Complex Korean Medical Treatment

Background: Diabetic polyneuropathy is the most common complication in diabetics, occurring in 50% of all cases. About 10-20% of all diabetics are accompanied by neurological pain, showing a tendency to increase with age. Clinical aspects are very diverse, from mild abnormalities on nerve conduction tests to severe abnormalities in all sensory, motor, and autonomic nerves; however, sensory symptoms usually precede motor symptoms. Patients typically express sensory symptoms, such as positive and negative symptoms, which decrease the quality of life and have marked clinical implications, such as increased morbidity and mortality. Although Western medical drugs, such as tricyclic antidepressants, anticonvulsants, and narcotic analgesics, are used for diabetic polyneuropathy, a standard treatment has not been established.Case report: A 65-year-old male with paresthesia and pain due to diabetic polyneuropathy was treated with &lt;i&gt;Uchashinki-hwan&lt;/i&gt;, acupuncture, electroacupuncture, moxibustion, and Jungsongouhyul pharmacopuncture for 10 days. We used the Toronto Clinical Neuropathy Scoring System, EuroQol-5 Dimension, and Visual Analog Scale to evaluate symptoms. Subsequently, the Neuropathy Scoring System, EuroQol-5 Dimension, and subjective discomfort improved.Conclusion: The present case report suggests that combined Korean medicine treatment might be an effective treatment for paresthesia and pain with diabetic polyneuropathy. Several follow-up studies should be conducted to clarify the effectiveness of the treatment.

RNA-Seq Reveals Sex Differences in Gene Expression during Peripheral Neuropathic Inflammation and in Pain Relief from a COX-2 Inhibiting Theranostic Nanoemulsion.

Given decades of neuroinflammatory pain research focused only on males, there is an urgent need to better understand neuroinflammatory pain in females. This, paired with the fact that currently there is no long-term effective treatment for neuropathic pain furthers the need to evaluate how neuropathic pain develops in both sexes and how it can be relieved. Here we show that chronic constriction injury of the sciatic nerve caused comparable levels of mechanical allodynia in both sexes. Using a COX-2 inhibiting theranostic nanoemulsion with increased drug loading, both sexes achieved similar reduction in mechanical hypersensitivity. Given that both sexes have improved pain behavior, we specifically explored differential gene expression between sexes in the dorsal root ganglia (DRG) during pain and relief. Total RNA from the DRG revealed a sexually dimorphic expression for injury and relief caused by COX-2 inhibition. Of note, both males and females experience increased expression of activating transcription factor 3 (Atf3), however, only the female DRG shows decreased expression following drug treatment. Alternatively, S100A8 and S100A9 expression appear to play a sex specific role in relief in males. The sex differences in RNA expression reveal that comparable behavior does not necessitate the same gene expression.

Machine Learning in Spinal Cord Stimulation for Chronic Pain.

Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. The success of SCS is dependent on candidate selection, response to trialing, and programming optimization. Owing to the subjective nature of these variables, machine learning (ML) offers a powerful tool to augment these processes. Here we explore what work has been done using data analytics and applications of ML in SCS. In addition, we discuss aspects of SCS which have narrowly been influenced by ML and propose the need for further exploration. ML has demonstrated a potential to complement SCS to an extent ranging from assistance with candidate selection to replacing invasive and costly aspects of the surgery. The clinical application of ML in SCS shows promise for improving patient outcomes, reducing costs of treatment, limiting invasiveness, and resulting in a better quality of life for the patient.

Increasing the Passive Range of Joint Motion in Stroke Patients Using Botulinum Toxin: The Role of Pain Relief.

By blocking the release of neurotransmitters, botulinum toxin A (BoNT-A) is an effective treatment for muscle over-activity and pain in stroke patients. BoNT-A has also been reported to increase passive range of motion (p-ROM), the decrease of which is mainly due to muscle shortening (i.e., muscle contracture). Although the mechanism of action of BoNT-A on p-ROM is far from understood, pain relief may be hypothesized to play a role. To test this hypothesis, a retrospective investigation of p-ROM and pain was conducted in post-stroke patients treated with BoNT-A for upper limb hypertonia. Among 70 stroke patients enrolled in the study, muscle tone (Modified Ashworth Scale), pathological postures, p-ROM, and pain during p-ROM assessment (Numeric Rating Scale, NRS) were investigated in elbow flexors (48 patients) and in finger flexors (64 patients), just before and 3-6 weeks after BoNT-A treatment. Before BoNT-A treatment, pathological postures of elbow flexion were found in all patients but one. A decreased elbow p-ROM was found in 18 patients (38%). Patients with decreased p-ROM had higher pain-NRS scores (5.08 ± 1.96, with a pain score ≥8 in 11% of cases) than patients with normal p-ROM (0.57 ± 1.36) (p < 0.001). Similarly, pathological postures of finger flexion were found in all patients but two. A decreased finger p-ROM was found in 14 patients (22%). Pain was more intense in the 14 patients with decreased p-ROM (8.43 ± 1.74, with a pain score ≥ 8 in 86% of cases) than in the 50 patients with normal p-ROM (0.98 ± 1.89) (p < 0.001). After BoNT-A treatment, muscle tone, pathological postures, and pain decreased in both elbow and finger flexors. In contrast, p-ROM increased only in finger flexors. The study discusses that pain plays a pivotal role in the increase in p-ROM observed after BoNT-A treatment.

Combined Programmed Intermittent Bolus and Patient-Controlled Bolus Is a More Favorable Setting for Epidural Pain Relief Than Continuous Infusion.

Epidural analgesia is a suitable and effective treatment for labor pain. However, the preferable modality setting for delivery remains debatable. This study adopted a programmed intermittent epidural bolus (PIEB) setting in conjunction with a patient-controlled epidural analgesia (PCEA) setting to improve the quality of labor analgesia and reduce the number of medical staff. We conducted a prospective observational analysis of primigravida parturients scheduled for spontaneous labor, which required epidural analgesia for painless labor. A total of 483 healthy primigravida parturients with singleton pregnancies were included in this cohort; 135 nulliparous patients were assigned to the continuous infusion setting (CEI) group and 348 to the PIEB + PCEA group. Compared to the CEI setting, the PIEB + PCEA setting significantly reduced the manual rescue by the clinician, extended the time required for the first manual rescue dose, and acclaimed good maternal satisfaction. The use of the CEI mode increased for poor performance requiring more than two rescues with an odds ratio of 2.635 by a binary logistic regression analysis. Using the PIEB + PCEA setting as the maintenance infusion had a longer duration for the first requested manual rescue, fewer manual rescue boluses, excellent satisfaction, and no significant increase in adverse events compared to the CEI setting.

Effectiveness of music therapy within community hospitals: an EMMPIRE retrospective study.

Given the challenges health systems face in providing effective nonpharmacologic treatment for pain and psychological distress, clinical effectiveness studies of evidence-based strategies such as music therapy (MT) are needed. This study examined changes in patient-reported outcomes (PROs) after MT and explored variables associated with pain reduction of ≥2 units on a 0 to 10 numeric rating scale (NRS). A retrospective review was conducted on initial MT interventions provided to adults receiving community hospital care between January 2017 and July 2020. Sessions were included if participants reported pre-session pain, anxiety, and/or stress scores of ≥4 on the NRS. Data analysis included a bootstrap analysis of single-session changes in PROs and a logistic regression exploring variables associated with pain reduction (ie, ≥2 units vs <2 units). Patients (n = 1056; mean age: 63.83 years; 76.1% female; 57.1% White; 41.1% Black/African American) reported clinically significant mean reductions in pain (2.04 units), anxiety (2.80 units), and stress (3.48 units). After adjusting for demographic, clinical, and operational characteristics in the model (c-statistic = 0.668), patients receiving an MT session in which pain management was a goal were 4.32 times more likely (95% confidence interval 2.26, 8.66) to report pain reduction of ≥2 units than patients receiving an MT session in which pain management was not a session goal. This retrospective study supports the clinical effectiveness of MT for symptom management in community hospitals. However, additional research is needed to determine which characteristics of MT interventions and patients influence pain change.

Molecular and Epigenetic Aspects of Opioid Receptors in Drug Addiction and Pain Management in Sport.

Opioids are substances derived from opium (natural opioids). In its raw state, opium is a gummy latex extracted from Papaver somniferum. The use of opioids and their negative health consequences among people who use drugs have been studied. Today, opioids are still the most commonly used and effective analgesic treatments for severe pain, but their use and abuse causes detrimental side effects for health, including addiction, thus impacting the user's quality of life and causing overdose. The mesocorticolimbic dopaminergic circuitry represents the brain circuit mediating both natural rewards and the rewarding aspects of nearly all drugs of abuse, including opioids. Hence, understanding how opioids affect the function of dopaminergic circuitry may be useful for better knowledge of the process and to develop effective therapeutic strategies in addiction. The aim of this review was to summarize the main features of opioids and opioid receptors and focus on the molecular and upcoming epigenetic mechanisms leading to opioid addiction. Since synthetic opioids can be effective for pain management, their ability to induce addiction in athletes, with the risk of incurring doping, is also discussed.

Systemic and Peripheral Mechanisms of Cortical Stimulation-Induced Analgesia and Refractoriness in a Rat Model of Neuropathic Pain.

Epidural motor cortex stimulation (MCS) is an effective treatment for refractory neuropathic pain; however, some individuals are unresponsive. In this study, we correlated the effectiveness of MCS and refractoriness with the expression of cytokines, neurotrophins, and nociceptive mediators in the dorsal root ganglion (DRG), sciatic nerve, and plasma of rats with sciatic neuropathy. MCS inhibited hyperalgesia and allodynia in two-thirds of the animals (responsive group), and one-third did not respond (refractory group). Chronic constriction injury (CCI) increased IL-1β in the nerve and DRG, inhibited IL-4, IL-10, and IL-17A in the nerve, decreased β-endorphin, and enhanced substance P in the plasma, compared to the control. Responsive animals showed decreased NGF and increased IL-6 in the nerve, accompanied by restoration of local IL-10 and IL-17A and systemic β-endorphin. Refractory animals showed increased TNF-α and decreased IFNγ in the nerve, along with decreased TNF-α and IL-17A in the DRG, maintaining low levels of systemic β-endorphin. Our findings suggest that the effectiveness of MCS depends on local control of inflammatory and neurotrophic changes, accompanied by recovery of the opioidergic system observed in neuropathic conditions. So, understanding the refractoriness to MCS may guide an improvement in the efficacy of the technique, thus benefiting patients with persistent neuropathic pain.

A standardized anesthetic/analgetic regimen compared to standard anesthetic/analgetic regimen for patients with high-risk factors undergoing open lumbar spine surgery: a prospective comparative single-center study.

The objective of the study is to improve the results of patients undergoing lumbar spine surgery who are at high risk for anesthesia and/or surgical complications. Two independent groups were compared: the study group (SG, n = 40) (standardized neuroanesthetic protocol with multimodal analgesia) and the control group (CG, n = 40) (intravenous anesthesia based on propofol and fentanyl). The data were collected using prospective observation of early and long-term results of lumbar fusion. After 24months, the level of functional state and quality of life were studied. Patients in the SG did not have statistically significant changes in intraoperative hemodynamics; the best indicators of cognitive functions were noted. The effectiveness of the SG compared with the CG was confirmed by a statistically significantly lower amount of perioperative opioid drugs required (p = 0.01) and a minimal level of incisional pain (p < 0.05). An intergroup comparison of the adverse effects of anesthesia revealed a significantly lower number in the SG (n = 4) compared to the CG (n = 16) (p = 0.004). The number of postoperative surgical complications was comparable (p = 0.72). Intergroup comparison showed improved ODI, SF-36, and the Macnab scale at 24months after surgery in the SG compared to the CG (p < 0.05). Long-term clinical results correlated with the level of incisional pain in the first three postoperative days. Our standardized neuroanesthetic protocol ensured effective treatment of postoperative incisional pain, significantly decreased the perioperative use of opioids, reduced adverse anesthesia events, and improved long-term clinical results in patients with high risk factors for anesthetic complications who undergoing open lumbar spine surgery.

Comparison of Tertiary Drug Information Resources With the CDC Guideline for Oxycodone Dosing: Are Patients at Risk?

Background: Inappropriate prescribing of opioids is thought to play a central role in the ongoing opioid health crisis. Tertiary information resources are commonly used by clinicians for obtaining opioid dosing information. To assist health care providers in pain management, the Centers for Disease Control and Prevention (CDC) developed a guideline for prescribing opioids. Objective: To identify discrepancies for dosing information on oxycodone between commonly used tertiary drug information resources and the CDC Guideline. Methods: Searches of the tertiary drug information resources were conducted in the following order: Facts and Comparisons, Lexicomp, Medscape, and Micromedex. The term "oxycodone" was entered in the search box in the tertiary resources' applications. Drug information items retrieved were organized in tabular format. In the Google Chrome version 106.0.5249.119 search box, the term "CDC guideline for opioid dosing" was entered to retrieve current information on the CDC Guideline. Results: Searches produced drug information on oxycodone for available formulations, dosing regimens, recommended dosing, and maximum daily dose (MDD). Searches revealed discrepancies in dosing recommendations for oxycodone among tertiary drug resources and between tertiary drug resources and the CDC Guideline. Conclusions: When considering maximum daily dosing information for oxycodone from the selected tertiary drug information resources, the potential exists for patients to be at risk of addiction, overdose, and perhaps death. Improving the way opioids are prescribed through the CDC Clinical Practice Guideline can ensure patients have access to safer, more effective chronic pain treatment while reducing the number of people who misuse or overdose from inappropriate dosing information.

Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety.

Chronic pain is long-lasting pain that often persists during chronic diseases or after recovery from disease or injury. It often causes serious side effects, such as insomnia, anxiety, or depression which negatively impacts the patient's overall quality of life. Serotonin (5-HT) in the central nervous system (CNS) has been recognized as an important neurotransmitter and neuromodulator which regulates various physiological functions, such as pain sensation, cognition, and emotions-especially anxiety and depression. Its widespread and diverse receptors underlie the functional complexity of 5-HT in the CNS. Recent studies found that both chronic pain and anxiety are associated with synaptic plasticity in the anterior cingulate cortex (ACC), the insular cortex (IC), and the spinal cord. 5-HT exerts multiple modulations of synaptic transmission and plasticity in the ACC and the spinal cord, including activation, inhibition, and biphasic actions. In this review, we will discuss the multiple actions of the 5-HT system in both chronic pain and injury-related anxiety, and the synaptic mechanisms behind them. It is likely that the specific 5-HT receptors would be new promising therapeutic targets for the effective treatment of chronic pain and injury-related anxiety in the future.