Acupuncture for radicular pain: a review of analgesic mechanism.

Radicular pain, a common and complex form of neuropathic pain, presents significant challenges in treatment. Acupuncture, a therapy originating from ancient traditional Chinese medicine and widely utilized for various pain types, including radicular pain, has shown promising outcomes in the management of lumbar radicular pain, cervical radicular pain, and radicular pain due to spinal stenosis. Despite its efficacy, the exact mechanisms through which acupuncture achieves analgesia are not fully elucidated and are the subject of ongoing research. This review sheds light on the current understanding of the analgesic mechanisms of acupuncture for radicular pain, offering valuable perspectives for both clinical application and basic scientific research. Acupuncture is postulated to relieve radicular pain by several mechanisms: peripherally, it reduces muscle spasms, lessens mechanical pressure on nerve roots, and improves microcirculation; at the molecular level, it inhibits the HMGB1/RAGE and TLR4/NF-κB signaling pathways, thereby decreasing the release of pro-inflammatory cytokines; within the spinal cord, it influences synaptic plasticity; and centrally, it modulates brain function, particularly affecting the medial prefrontal cortex, anterior cingulate cortex, and thalamus within the default mode network. By acting across these diverse biological domains, acupuncture presents an effective treatment modality for radicular pain, and deepening our understanding of the underlying mechanisms regarding analgesia for radicular pain is crucial for enhancing its clinical efficacy and advancement in pain management.

N-Acetyl Cysteine as an Add-on Therapy is Useful in Treating Acute Lumbar Radiculopathy Caused by Disc Herniation: Results of a Randomized, Controlled Clinical Trial.

BACKGROUND: Available experimental and clinical evidence indicates that N-Acetyl cysteine (NAC) may have an analgesic role in specific pain conditions, particularly neuropathic pain. Thus, we hypothesized that NAC supplementation might be also helpful in decreasing pain and improving pain-related disability in patients with acute radiculopathy. We designed this study to investigate the potential use of NAC-adjunctive treatment to Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) in patients with acute radiculopathy secondary to lumbar intervertebral disc herniation. METHODS: Sixty-two patients diagnosed with acute lumbar radiculopathy associated with disc herniation were randomly allocated to the NAC or the placebo groups. Besides naproxen at a dose of 500 mg twice a day, participants based on their allocation group started with NAC or matched placebo at a dose of 600 mg twice a day for eight weeks. The pain severity, measured by the Visual Analog Scale (VAS), and pain-related disability measured by the Oswestry Disability Index (ODI) were measured at baseline and weeks 2, 4, and 8 of treatment. Global improvement of symptoms rated by Patient and Clinical Global Impressions of Change (PGIC and CGIC) was also recorded at the end of week 8. All analyses were conducted on an Intentionto- Treat (ITT) analysis data set. RESULTS: A comparison of the VAS and ODI scores at weeks 2 and 4 of the treatment between the two groups did not show a significant difference. In contrast, from week 4 to week 8, we noticed a significantly greater reduction in the mean VAS and ODI scores in the NAC group compared to the placebo group (p-value <0.001 for both variables). In parallel with these results, also, more NAC-treated than placebo-treated patients achieved treatment success defined as ''very much'' or ''much improved'' on CGIC and PGIC scales, and these differences reached a significant level (p-value = .011 and p-value = .043). CONCLUSIONS: This study suggested that NAC might be a relevant candidate for adjunct therapy in managing acute lumbar radiculopathy. Additional clinical trials are needed to validate these findings.

Alpha-Lipoic Acid, Palmitoylethanolamide, Myrrh, and Oxygen-Ozone Therapy Improve Pharmacological Therapy in Acute Painful Lumbosacral Radiculopathy due to Herniated Disc.

BACKGROUND: Neuropathic mechanisms largely contribute to radicular Low Back Pain (LBP) and an increase in oxidative stress is recognized as one of the possible causes of nerve damage, inducing axonal degeneration and myelin degradation of nerve fibers. OBJECTIVES: We investigated whether a combination of nutraceutical supplements and oxygen-ozone (O2-O3) therapy might reduce disability and improve clinical effects of pharmacological therapy in patients with acute radicular LBP. STUDY DESIGN: This is a prospective, open-label, comparative observational study approved by the Institutional Review Board of the Sapienza University of Rome (RS 6285/2021). SETTING: Physical Medicine and Rehabilitation Unit of Sant'Andrea Hospital. METHODS: Within the scope of this study, 62 patients with acute radicular LBP diagnosed with disc herniation were assigned into 4 groups. The first group was assigned pharmacological therapy (n = 16), the second group was assigned pharmacological therapy and nutraceutical supplements (n = 15), the third group was assigned pharmacological therapy and O2-O3 therapy (n = 15), and the fourth group was assigned pharmacological therapy, nutraceutical supplements, and O2-O3therapy (n = 16). All patients who participated in the study were evaluated at the beginning of the study, 2 weeks, and 4 weeks (T2) after the beginning of treatment using the Numeric Rating Scale (NRS-11), Oswestry Disability Index (ODI), and 12-item Short-Form Health Survey. Opioid analgesic intake was noted from baseline to end of treatment (T2). RESULTS: In each group was observed a statistically significant difference for all measures compared to the baseline. At the T2 evaluation time between groups for the Mann-Whitney U test, a statistically significant difference was found: in the ODI scale between groups B and A (P = 0.004), groups C and A (P < 0.001), and groups D and A (P < 0.001); in the NRS-11 between groups B and A (P = 0.017), groups C and A (P = 0.002), and groups D and A (P < 0.001); in the 12-item Physical Component Summary score between groups B and A (P = 0.003), groups C and A (P = 0.002), and groups D and A (P < 0.001), while no significant differences between groups were observed in the 12-item Mental Component Summary score. The average days of opioid usage were similar in the 4 groups (8.33 in group A, 8.33 in group B, 8.33 in group C, and 8.75 in group D). However, the percentage of patients requiring adjuvant opioid therapy differed remarkably: 60% in group A, 40% in group B, 20% in group C, and 25% in group D. LIMITATIONS: A small number of patients were recruited, and we did not perform long-term follow-up. CONCLUSIONS: This study supports a multimodal approach combining nutraceutical supplements and O2-O3 therapy with pharmacological therapy in the treatment of acute radicular LBP secondary to disc herniation. The combination of neurotrophic and antioxidant therapies represents an etiopathogenetic approach, not purely symptomatic, that reduces symptomatology and avoids progression of the nerve damage.

Lysine-specific demethylase 1 in primary sensory neurons participates in chronic compression of dorsal root ganglion-induced neuropathic pain.

Low back and radicular pain syndromes, usually caused by local inflammation and irritation to the nerve root and dorsal root ganglion (DRG), are common throughout medical practice, but sufficient pain relief is scarce. In this study, we employed a chronic compression of DRG (CCD)-induced radicular pain model in rats to explore whether lysine-specific demethylase 1 (LSD1), a histone demethylase and transcriptional co-repressor, is involved in the pathological process of radicular pain. We found that LSD1 was expressed in various-sized DRG neurons by immunohistochemistry. CCD induced the upregulation of LSD1 in compressed L4-L5 DRGs. Moreover, either LSD1 small interfering RNAs or LSD1 inhibitor attenuated CCD-induced pain hypersensitivities. LSD1 was also upregulated in the injured lumbar 4 (L4) DRG in a spinal nerve ligation (SNL)-induced neuropathic pain mouse model. Nevertheless, LSD1 was not altered in L3-L5 DRGs in complete Freund's adjuvant-induced inflammatory pain mouse model, paclitaxel- or streptozotocin-induced neuropathic pain models. Furthermore, knockdown of LSD1 in the injured L4 DRG reversed SNL-induced pain hypersensitivities in mice. Therefore, we speculate that nerve injury induced the upregulation of LSD1 in the injured DRGs, which contributes to neuropathic pain hypersensitivities; thus, LSD1 may serve as a potential target for the treatment of radicular pain and neuropathic pain.

Hyperpolarization-activated cyclic nucleotide-gated 2 contributes to electroacupuncture analgesia on lumbar disc herniation-induced radicular pain through activation of microglia in spinal dorsal horn.

OBJECTIVE: To explore the mechanisms of dorsal root ganglia and spinal microglia cascade cross in electroacupuncture (EA) analgesia in the treatment of lumbar disc herniation. METHODS: A rat model of lumbar disc herniation (LDH) was established, EA was administered at Huantiao (GB30) acupoint 30 min once a day, for 3 d. Before and after modeling, and after EA, mechanical allodynia thresholds were detected. Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) in dorsal root ganglia was detected by quantitative polymerase chain reaction (qPCR) and Western blot. C-X3-C motif chemokine ligand 1 (CX3CL1) and activity of microglia in spinal cord was observed separately qPCR and immunofluorescence staining. RESULTS: The mechanical allodynia threshold of the right planta of model rats was significantly reduced ( < 0.01), EA increased the mechanical pain threshold of rats ( < 0.01), and decreased HCN2 mRNA, and protein expression, reduced the expression of CX3CL1 and the activation of microglia. ZD7288 (a blocker of HCN channel) reduced the analgesic effect of EA from 1.83 ± 0.84 to 0.74 ± 0.20 ( < 0.05), and the expression of CX3CL1 in the spinal cord decreased from 0.52 ± 0.11 to 0.15 ± 0.05 ( < 0.01). CONCLUSION: EA analgesia on the radicular pain of LDH is definite. EA reduced the expression of HCN2 channel in the dorsal root ganglion, thereby decreasing the noxious stimulation entered to microglia in spinal dorsal horn. Our work supports EA is an effective treatment for radicular pain of LDH.

Intradiscal oxygen-ozone therapy for the treatment of symptomatic lumbar disc herniation: A preliminary study.

PURPOSE: To assess safety and effectiveness of computed tomography (CT)-guided intradiscal oxygen-ozone therapy (O2-O3 therapy) for the treatment of symptomatic lumbar disc herniation and radiological changes. MATERIALS AND METHODS: This study was conducted in twenty patients presenting lumbar disc herniation with resistant lumbar or lumbar radicular pain They underwent intradiscal oxygen-ozone therapy under CT guidance. They were treated at one- or two-disc levels, representing a total of 24 discs treated. MR imaging examinations were obtained before treatment and 2 months post-procedure to analyse treatment-related disc modifications including modification of the surfaces of the disc and of the herniated disc, and the variations in disc height according to the disc height index. Clinical outcomes were assessed using the visual analogue scale (VAS) to evaluate the severity of pain before the procedure, at primary (2 months) and at secondary (12 months) follow-ups. RESULTS: All the procedures were technically successful. The median VAS scores were 7.95 before the procedure, 3.9 at 2 months and 2.95 at 12 months. MRI analysis showed a significant decrease in herniation size at 2 months (-20%, p = 0.008). No immediate or late complications were observed. Only three patients (13.6%) underwent lumbar spine microdiscectomy in the year following ozone therapy. The treatment appeared to be more effective in cases of nerve root symptomatology. CONCLUSION: This study suggests that intradiscal O2-O3 therapy is safe and effective for the treatment of lumbar disc herniation associated with resistant lumbar or lumbar radicular pain.

Asymmetry of Cervical Multifidus and Longus Colli Muscles Size in Participants With and Without Cervical Radicular Pain.

OBJECTIVES: The aim of this study was to determine the asymmetry of cervical multifidus (MF) and longus colli (LC) muscles in patients with unilateral chronic radicular neck pain (CRNP) and healthy subjects using ultrasonography. MATERIALS AND METHODS: Ninety five individuals (50 patients with unilateral CRNP and 45 healthy subjects) participated in this study. The size of the cervical MF and LC muscles; anterior posterior dimension (APD) and lateral dimension (LD); were bilaterally measured in a relaxed state using ultrasonography. RESULTS: Patients with CRNP showed greater asymmetry in the cervical MF and LC muscles size than the healthy subjects. The mean percentages differences between sides for MF and LC muscles size was higher in patients than that of healthy subjects (for both APD and LD; P<0.05). The ratio of smaller to larger dimensions of the cervical MF and LC muscles for patients were significantly less than that of healthy controls (for both APD and LD; P< 0.05). CONCLUSION: The results indicated that cervical MF and LC muscles showed higher asymmetry between sides and lesser ratio of smaller size to larger size in patients with CRNP as compared with healthy subjects. Current results confirmed the presence of MF and LC muscles atrophy in subjects with CRNP.

Regenerative Medicine for Axial and Radicular Spine-Related Pain: A Narrative Review.

INTRODUCTION: Regenerative injection-based therapy has established itself as a therapeutic option for the management of a variety of painful musculoskeletal conditions. The aim of this work was to review the current literature regarding regenerative injection therapy for axial/radicular spine pain. METHODS: A comprehensive literature review was conducted on the use of regenerative medicine for axial/radicular spine pain. Eligible articles analyzed the therapeutic injection effects of platelet-rich plasma (PRP), prolotherapy, or mesenchymal signaling cells (MSCs) via intradiscal, facet joint, epidural, or sacroiliac joint delivery. RESULTS: Regarding intradiscal PRP, there are level I/IV studies supporting its use. Regarding intradiscal prolotherapy, there are level III to IV studies supporting its use. Regarding intradiscal MSCs, there are level I/IV studies supporting its use with the exception of one level IV study that found no significant improvement at 12 months. Regarding facet joint injections with PRP, there are level I/IV studies supporting its use. Regarding facet joint injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate any statistical significance supporting its use. Regarding epidural injections with PRP, there are level I/IV studies supporting its use. Regarding epidural injections with prolotherapy, there are level IV studies supporting its use, though the one level I study did not demonstrate statistical significance beyond 48 hours. Regarding sacroiliac joint injections with PRP, there are level I/IV studies supporting its use. Regarding sacroiliac joint injections with prolotherapy, there are level I/III studies supporting its use. CONCLUSIONS: Currently, there are level I studies to support the use of PRP and MSC injections for discogenic pain; facet joint injections with PRP; epidural injections of autologous conditioned serum and epidural prolotherapy; and PRP and prolotherapy for sacroiliac joint pain. One level I study showed that facet joint prolotherapy has no significant benefit. Notably, no intervention has multiple published level I studies.

Puerarin alleviate radicular pain from lumbar disc herniation by inhibiting ERK-dependent spinal microglia activation.

Lumbar disc herniation is a common cause of radicular pain, but the mechanism remains ambiguous and the treatment stays unsatisfied. Many studies revealed a traditional Chinese medicine puerarin may moderate chronic pain from diabetes and nerve injury. Thus far, the role and mechanism of puerarin in radicular pain is still unknown. In this study, by using a rat model of lumbar disc herniation, which was induced by autologous nucleus pulposus (NP) implantation, the analgesic effect of puerarin on radicular pain was tested. Puerarin was delivered intraperitoneally form 1 h before surgery, and once daily for 7 days. The results demonstrated that NP implantation induced long-lasting pain, characterized by decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in ipsilateral hindpaws, as long as day 20 after surgery. Spinal phosphorylated extracellular signal-regulated kinase (p-ERK) was up-regulated from day 5 to day 20 after surgery in ipsilateral but not contralateral side, and p-ERK was mainly co-localized with microglia. Puerarin decreased p-ERK expression from day 7 to day 20 after surgery. Puerarin or ERK inhibitor PD98059 alleviated pain behaviors, decreased expression of microglia marker ionized calcium-binding adaptor molecule 1 (Iba-1) in rats with NP implantation. The results suggested puerarin may alleviate radicular pain by inhibiting ERK-dependent or accompanied spinal microglia activation.

Osteopathic manipulative treatment in chronic coccydynia: A case series.

BACKGROUND: Coccydynia is a disorder associated with pain/discomfort at the base of the spine. The role of osteopathic manipulative treatment (OMT) in chronic coccydynia as well as for low back pain (LBP) and radicular pain (RP) associated with coccydynia, has not previously been investigated. This study seeks to analyse the effects of OMT on chronic coccydynia compared to physical therapy and pharmacological treatment (PTPT). The secondary objective is to analyse the effect of OMT on LBP and RP associated with coccydynia. METHODS: Clinical records of 50 patients were examined. These patients (aged 39.94 ± 15.34 years, BMI 21.22 ± 3.15) who complained of chronic coccydynia were assessed 3 times: before any treatment (t0), after PTPT (t1) and after OMT (t2). Patients were treated with PTPT during the first 3 months and then referred by physicians to osteopaths to receive 3 sessions of OMT over a period of 5 weeks. The outcome measurements were made by a visual analogue scale (VAS 0-10 cm) and the Oswestry Low Back Pain Disability Questionnaire. RESULTS: Before starting OMT treatment, patients showed a stable condition of coccydynia (mean VAS values from 7.1 to 6.5 p = 0.065) and a slight but significant reduction in disability (mean OD values from 17.7 to 14.5 p = 0.017) after PTPT. After the 3 sessions of OMT, all subjects gained a successful reduction in pain (mean VAS values from 6.5 to 1.2, p ≤ 0.001) and demonstrated a higher significant reduction in disability (mean Oswestry scale values from 14.5 to 2.5, p < 0.001). CONCLUSIONS: This case series shows that OMT elicits a positive benefit for pain relief and reduction in disability in patients complaining of coccydynia (with or without LBP and RP associated with coccydynia). Therefore, OMT could be considered as a valid therapeutic approach for treating chronic coccydynia. Nevertheless, further research is required to test the hypothesis and to better determine the benefits of OMT.

Massive Lumbar Disk Herniation Following "Therapeutic" Water Boiling of the Lower Extremities: Case Report and Literature Review.

BACKGROUND: Legs burning for treating lumbar radicular pain are still in use nowadays in low socioeconomical environments. They are dangerous as the case we report shows clearly. CLINICAL CASE: A 49-year-old man came to our attention with severe flaccid paraparesis occurred 10 days before, almost immediately after he had immersed his legs in boiling water to treat his severe left lumbocrural pain. This was known to be due to a right L3/4 herniated disk diagnosed by magnetic resonance imaging. At the examination he showed severe motor paresis and absent reflexes of his lower limbs, while crural pain was mild and sensation and urinary function were unaffected. The results of his neurologic examination led us to suspect an acute motor axon degeneration related to thermal shock. Lumbar magnetic resonance imaging, performed before the planned electromyogram as an exception to the established routine, showed instead a giant 5- × 5.5-cm, herniated disk compressing the dural sac at L3. CONCLUSIONS: Prompt surgical decompression led to rapid improvement. We discuss here the pathophysiology of this unusual case and point out how medieval practices for treating sciatica-like pain are not only unjustified from a medical viewpoint but also potentially dangerous.

Effectiveness of neural mobilization in patients with spinal radiculopathy: a critical review.

Spinal radiculopathy (SR) is a multifactorial nerve root injury that can result in significant pain, psychological stress and disability. It can occur at any level of the spinal column with the highest percentage in the lumbar spine. Amongst the various interventions that have been suggested, neural mobilization (NM) has been advocated as an effective treatment option. The purpose of this review is to (1) examine pathophysiological aspects of spinal roots and peripheral nerves, (2) analyze the proposed mechanisms of NM as treatment of injured nerve tissues and (3) critically review the existing research evidence for the efficacy of NM in patients with lumbar or cervical radiculopathy.