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21 pages, 2330 KiB

Open AccessArticle

NADA Ear Acupuncture and Medical Acupuncture for Pain- and Health-Related Quality of Life among Older Patients with Chronic Nonspecific Low Back Pain: A Prospective Clinical Trial

by Monika Rybicka, Jerzy Gąsowski, Anna Przeklasa-Muszyńska, Jan Dobrogowski, Jagoda Wierzbicka, Ka-Kit Hui, Sara Ptasnik and Magdalena Kocot-Kępska

Brain Sci. 2024, 14(3), 205; https://doi.org/10.3390/brainsci14030205 - 23 Feb 2024

Viewed by 2906

Abstract

Background: The purpose of this study was to investigate the efficacy and safety of the NADA (National Acupuncture Detoxification Association)-standardized ear acupuncture protocol in comparison to medical acupuncture (MA) in the treatment of chronic nonspecific low back pain (LBP) in older adults. Methods: [...] Read more.

Background: The purpose of this study was to investigate the efficacy and safety of the NADA (National Acupuncture Detoxification Association)-standardized ear acupuncture protocol in comparison to medical acupuncture (MA) in the treatment of chronic nonspecific low back pain (LBP) in older adults. Methods: This was a prospective, clinical, single center, open label, comparative study. A total of 60 older patients with chronic nonspecific LBP were enrolled in the study. The patients were divided into two groups. The MA group received treatment with medical acupuncture (MA), while the NADA group received NADA ear acupuncture once a day for 20 min, for a total of 10 sessions. The co-primary outcome measures were the reduction in pain intensity evaluated by the Numeric Rating Scale (NRS) compared to baseline and improvement in patients’ quality of life (QOL) assessed in the SF-36 questionnaire before and after treatment; this was compared between the two groups. Results: After two weeks of treatment, a significant reduction compared to baseline was observed in the NRS scores following treatment with medical acupuncture as well as after the utilization of NADA ear acupuncture protocol: NRS score for average pain experienced by the patients over the previous week (NRSa) MA: p = 0.002; NADA: p < 0.001, maximum NRS score in the past week (NRSm) MA: p < 0.001; NADA: p < 0.001, and NRS score at the time of examination (NRSe) MA: p = 0.001; NADA: p < 0.001. Reduction of the NRSa score compared to baseline was significantly greater in the NADA group (p = 0.034). Significant improvements in the QOL of patients according to the SF-36 questionnaire compared to baseline were observed in the MA group in the following domains: PF (p = 0.003), RP (p = 0.002), SF (p = 0.041), RE (p = 0.005), MH (p = 0.043), HT (p = 0.013), PCS (p = 0.004), and MCS (p = 0.025); and in the NADA group, in the following domains: PF (p = 0.004), RP (p = 0.048), BP (p = 0.001), VT (p = 0.035), RE (p = 0.006), MH (p < 0.001), HT (p = 0.003), PCS (p < 0.001), and MCS (p < 0.001). There were minor complications observed in 35% of patients (total of 20 participants); 31% (9 patients) in the MA group and 39% (11 patients) in the NADA group. These were minor and quickly resolved, including insertion point pain, minor bleeding after needle removal, and one instance of fainting. No patients in either group reported worsening of LBP. These complications occurred in 4.14% of MA sessions (12 times/290 sessions) and in 6.07% of NADA acupuncture sessions (16 times/280 sessions). Conclusion: The outcomes of this study suggest that both MA and NADA ear acupuncture could be a valuable and personalized component of a comprehensive approach to managing chronic nonspecific LBP in older patients. Incorporation of MA and NADA ear acupuncture into the clinical management of chronic nonspecific LBP in elderly patients has the potential to reduce pain intensity and improve the overall quality of life of affected individuals. However, further studies are needed to confirm our findings. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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Figure 1
Study timeline: T0: initial visit and pre-treatment evaluation; T1: 1 week after beginning of acupuncture sessions; T2: 2 weeks after beginning of acupuncture sessions, end of treatment; T3: final visit 3 weeks after beginning of acupuncture sessions, evaluation one week after completion of treatment; MA: Medical acupuncture; NADA: National Acupuncture Detoxification Association. Full article ">Figure 2
Number of participants in each study group: MA: Medical acupuncture; NADA: National Acupuncture Detoxification Association; N: number of patients. Full article ">Figure 3
Acupoints used in the MA and NADA groups; MA: Medical acupuncture; UB: Urinary Bladder; L: the level of lumbar vertebra; NADA: National Acupuncture Detoxification Association. Pictures of ear and back prepared in the program Canva (<a href="https://www.canva.com" target="_blank">https://www.canva.com</a>) (accessed on 15 July 2023). Full article ">Figure 4
Comparison of NRS Pain Scores Pre- and Post-Treatment in MA group NRS: Numeric Rating Scale; NRSe: NRS score at the time of examination; NRSm: maximum NRS score in the past week; NRSa: average pain experienced by the patients over the previous week. MA: Medical acupuncture. Statistically significant difference (p < 0.05); ** p < 0.01; *** p < 0.001 Full article ">Figure 5
Comparison of NRS Pain Scores Pre- and Post-Treatment in NADA group NRS: Numeric Rating Scale; NRSe: NRS score at the time of examination; NRSm: maximum NRS score in the past week; NRSa: average pain experienced by the patients over the previous week. NADA: National Acupuncture Detoxification Association. Statistically significant difference (p < 0.05), *** p < 0.001 Full article ">Figure 6
Comparison in QOL measures after treatment in the MA group The SF-36 questionnaire assesses quality of life (QOL) in 11 domains: PF: physical fitness; RP: role limitations due to physical problems; BP: bodily pain; GH: general health perception; VT: vitality; SF: social functioning; RE: role limitation due to emotional problems; MH: mental health; HT: health transition/change; PCS: total physical health; MCS: total mental health; PCS was calculated from RF, RP, BP and GH and MCS was calculated from VT, SF, RE, MH. MA: Medical acupuncture. * statistically significant difference (p < 0.05), ** p < 0.01. Full article ">Figure 7
Comparison of QOL measures after treatment in the NADA group. The SF-36 questionnaire assesses quality of life (QOL) in 11 domains: PF: physical fitness; RP: role limitations due to physical problems; BP: bodily pain; GH: general health perception; VT: vitality; SF: social functioning; RE: role limitation due to emotional problems; MH: mental health; HT: health transition/change; PCS: total physical health; MCS: total mental health; PCS was calculated from RF, RP, BP and GH and MCS was calculated from VT, SF, RE, MH. NADA: National Acupuncture Detoxification Association. * statistically significant difference (p < 0.05); ** p < 0.01; *** p < 0.001. Full article ">

13 pages, 1674 KiB

Open AccessArticle

Mu-Opioid Receptor 1 and C-Reactive Protein Single Nucleotide Polymorphisms as Biomarkers of Pain Intensity and Opioid Consumption

by Aleksander Turczynowicz, Piotr Jakubów, Karolina Niedźwiecka, Julia Kondracka, Weronika Pużyńska, Mariola Tałałaj, Tomasz Guszczyn, Paweł Grabala, Oksana Kowalczuk and Szymon Kocańda

Brain Sci. 2023, 13(12), 1629; https://doi.org/10.3390/brainsci13121629 - 24 Nov 2023

Cited by 2 | Viewed by 1419

Abstract

Children constitute a special group in pain therapy. Single nucleotide polymorphisms that are associated with differences in postoperative, inflammatory pain perception and opioid requirement are the A118G SNP in the mu-opioid receptor 1 (OPRM1) gene and the rs1205 CRP. This study aimed to [...] Read more.

Children constitute a special group in pain therapy. Single nucleotide polymorphisms that are associated with differences in postoperative, inflammatory pain perception and opioid requirement are the A118G SNP in the mu-opioid receptor 1 (OPRM1) gene and the rs1205 CRP. This study aimed to determine connection between OPRM1 and rs1205 CRP SNPs in pediatric patients postoperatively and pain intensity, the opioid dose needed to control pain after scoliosis correction, and other clinical aspects. Genotypes of rs1205 CRP and OPRM1 polymorphisms in a sample of 31 patients were specified, and statistical analysis was performed in terms of age, genotype frequency, pain assessment, sufentanil flow, post-anesthesia care unit stay, and the use of coanalgesics. The frequency of A/A and A/G genotypes in the OPRM1 gene was in line with 1000Genomes data for the European population. Patients from the AG group of OPRM1 SNP more frequently required coanalgesics for adequate pain control; however, it was of weak statistical significance. Other parameters measured in the study were not statistically significant in relation to OPRM1 and CRP polymorphisms. The effect of SNPs on postoperative pain management and opioid therapy in children was not confirmed by this study. An expansion of the study sample and other opioid-related SNPs is required. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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14 pages, 2315 KiB

Open AccessArticle

Low-Energy Transcranial Navigation-Guided Focused Ultrasound for Neuropathic Pain: An Exploratory Study

by Dong Hoon Shin, Seong Son and Eun Young Kim

Brain Sci. 2023, 13(10), 1433; https://doi.org/10.3390/brainsci13101433 - 8 Oct 2023

Cited by 4 | Viewed by 2355

Abstract

Neuromodulation using high-energy focused ultrasound (FUS) has recently been developed for various neurological disorders, including tremors, epilepsy, and neuropathic pain. We investigated the safety and efficacy of low-energy FUS for patients with chronic neuropathic pain. We conducted a prospective single-arm trial with 3-month [...] Read more.

Neuromodulation using high-energy focused ultrasound (FUS) has recently been developed for various neurological disorders, including tremors, epilepsy, and neuropathic pain. We investigated the safety and efficacy of low-energy FUS for patients with chronic neuropathic pain. We conducted a prospective single-arm trial with 3-month follow-up using new transcranial, navigation-guided, focused ultrasound (tcNgFUS) technology to stimulate the anterior cingulate cortex. Eleven patients underwent FUS with a frequency of 250 kHz and spatial-peak temporal-average intensity of 0.72 W/cm². A clinical survey based on the visual analog scale of pain and a brief pain inventory (BPI) was performed during the study period. The average age was 60.55 ± 13.18 years-old with a male-to-female ratio of 6:5. The median current pain decreased from 10.0 to 7.0 (p = 0.021), median average pain decreased from 8.5 to 6.0 (p = 0.027), and median maximum pain decreased from 10.0 to 8.0 (p = 0.008) at 4 weeks after treatment. Additionally, the sum of daily life interference based on BPI was improved from 59.00 ± 11.66 to 51.91 ± 9.18 (p = 0.021). There were no side effects such as burns, headaches, or seizures, and no significant changes in follow-up brain magnetic resonance imaging. Low-energy tcNgFUS could be a safe and noninvasive neuromodulation technique for the treatment of chronic neuropathic pain Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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Graphical abstract
Full article ">Figure 1
Diagram of participant recruitment and study design. Full article ">Figure 2
The process of administering low-energy focused ultrasound to a patient. (A) The fiducial marker and head gear are worn on the patient’s face and head, and the transducer is set. (B) The anterior cingulate cortex is targeted under the navigation guidance based on magnetic resonance imaging performed before the procedure. Once correct targeting is confirmed, planned sonication is performed. Full article ">Figure 3
Change of current pain degree according to the visual analog scale. The median average pain VAS at pre-procedure was 8.5 (range, 5.0–10.0), and this decreased to 6.0 (range, 2.0–9.0) immediately post-procedure, 6.0 (range, 2.0–9.0) at 2 weeks post-procedure, and 6.0 (range, 4.0–9.0) at 4 weeks post-procedure (p = 0.070, non-parametric Friedman test). The pre-procedure to 4 weeks post-procedure difference in average pain VAS was significant (mean difference 1.50 [95% CI, 0.41–2.59], p = 0.027, non-parametric Friedman test); however, other differences between each period were not significant (<a href="#brainsci-13-01433-t002" class="html-table">Table 2</a>, <a href="#brainsci-13-01433-f004" class="html-fig">Figure 4</a>). * p < 0.05 and ⸰ are lables that are out of range. Full article ">Figure 4
Change in average pain degree within the last 24 h according to the visual analog scale. * p < 0.05. Full article ">Figure 5
Change of maximum pain degree within the last 24 h according to the visual analog scale. * p < 0.05, ** p < 0.01, and ⸰ are lables that are out of range. Full article ">Figure 6
Change of sum of interference of daily life based on brief pain inventory. * p < 0.05 and ⸰ are lables that are out of range. Full article ">

13 pages, 281 KiB

Open AccessArticle

Prescription Trends in Complex Regional Pain Syndrome: A Retrospective Case–Control Study

by Suzanna Shermon, Kimberly M. Fazio, Richard Shim, Alaa Abd-Elsayed and Chong H. Kim

Brain Sci. 2023, 13(7), 1012; https://doi.org/10.3390/brainsci13071012 - 30 Jun 2023

Cited by 2 | Viewed by 1750

Abstract

Objective: The objective of this study was to evaluate discrepancies in prescription trends for analgesic medications in complex regional pain syndrome (CRPS) patients based on recommendations in the literature. Design: We conducted a retrospective case–control study. Subjects: A total of 2510 CRPS patients [...] Read more.

Objective: The objective of this study was to evaluate discrepancies in prescription trends for analgesic medications in complex regional pain syndrome (CRPS) patients based on recommendations in the literature. Design: We conducted a retrospective case–control study. Subjects: A total of 2510 CRPS patients and 2510 demographic-matched controls participated in this study. Methods: The SlicerDicer feature in Epic was used to find patients diagnosed with CRPS I or II between January 2010 and November 2022. An equal number of age-, gender-, and race-matched controls without a CRPS diagnosis were retracted from Epic. General and CRPS-associated prescription frequencies for the following classes were retrieved for both cases and controls: benzodiazepines, bisphosphonates, calcitonin, capsaicin, neuropathic pain medications, NSAIDs, opioids, and steroids. Results: A total of 740 (29%) CRPS patients and 425 (17%) controls were prescribed benzodiazepines (95% CI 0.1–0.15), 154 (6.1%) CRPS patients and 52 (2.1%) controls were prescribed capsaicin (95% CI 0.03–0.05), 1837 (73%) CRPS patients and 927 (37%) controls were prescribed neuropathic pain medications (95% CI 0.05–0.34), 1769 (70%) CRPS patients and 1217 (48%) controls were prescribed opioids (95% CI 0.19–0.25), 1095 (44%) CRPS patients and 1217 (48%) controls were prescribed steroids (95% CI 0.08–0.14), and 1638 (65%) CRPS patients and 1765 (70%) controls were prescribed NSAIDs (95% CI −0.08–0.02), p < 0.001 for all classes. With CRPS-associated prescriptions, (95% CI 0.05–0.16, p < 0.001) more CRPS patients were prescribed opioids (N = 398, 59%) than controls (N = 327, 49%). Conclusions: CRPS is difficult to treat with significant variance in suggested treatment modalities. Based on the results of our study, there is a divergence between some published recommendations and actual practice. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

16 pages, 1563 KiB

Open AccessArticle

Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain

by Magdalena Kocot-Kępska, Katarzyna Pawlik, Katarzyna Ciapała, Wioletta Makuch, Renata Zajączkowska, Jan Dobrogowski, Anna Przeklasa-Muszyńska and Joanna Mika

Brain Sci. 2023, 13(6), 858; https://doi.org/10.3390/brainsci13060858 - 25 May 2023

Cited by 3 | Viewed by 2557

Abstract

Neuropathic pain remains a clinical challenge due to its complex and not yet fully understood pathomechanism, which result in limited analgesic effectiveness of the management offered, particularly for patients with acute, refractory neuropathic pain states. In addition to the introduction of several modern [...] Read more.

Neuropathic pain remains a clinical challenge due to its complex and not yet fully understood pathomechanism, which result in limited analgesic effectiveness of the management offered, particularly for patients with acute, refractory neuropathic pain states. In addition to the introduction of several modern therapeutic approaches, such as neuromodulation or novel anti-neuropathic drugs, significant efforts have been made in the repurposing of well-known substances such as phenytoin. Although its main mechanism of action occurs at sodium channels in excitable and non-excitable cells and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level and how it influences morphine-induced analgesia have not been clarified, both being crucial from a clinical perspective. We demonstrated that single and repeated systemic administrations of phenytoin decreased tactile and thermal hypersensitivity in an animal model of neuropathic pain. Importantly, we observed an increase in the antinociceptive effect on thermal stimuli with repeated administrations of phenytoin. This is the first study to report that phenytoin improves morphine-induced antinociceptive effects and influences microglia/macrophage activity at the spinal cord and dorsal root ganglion levels in a neuropathic pain model. Our findings support the hypothesis that phenytoin may represent an effective strategy for neuropathic pain management in clinical practice, particularly when combination with opioids is needed. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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21 pages, 5321 KiB

Open AccessArticle

Comparison of Analgesic Efficacy between Epidural and Perineural Administration of Autologous Conditioned Serum in the Conservative Treatment of Low Back Pain Due to Lumbar Degenerative Disc Disease: A Randomized, Open-Label, Controlled Clinical Trial

by Piotr Godek, Beata Szczepanowska-Wolowiec and Dominik Golicki

Brain Sci. 2023, 13(5), 749; https://doi.org/10.3390/brainsci13050749 - 30 Apr 2023

Cited by 3 | Viewed by 2091

Abstract

Lumbar degenerative disc disease (LDDD) is widely acknowledged as a significant contributor to low back pain (LBP), which is a prevalent and debilitating health condition affecting millions of individuals worldwide. The pathogenesis of LDDD and associated pain mechanisms are thought to be mediated [...] Read more.

Lumbar degenerative disc disease (LDDD) is widely acknowledged as a significant contributor to low back pain (LBP), which is a prevalent and debilitating health condition affecting millions of individuals worldwide. The pathogenesis of LDDD and associated pain mechanisms are thought to be mediated by inflammatory mediators. Autologous conditioned serum (ACS, Orthokine) may be used for symptomatic treatment of LBP due to LDDD. This study aimed to compare the analgesic efficacy and safety of two routes of ACS administration, perineural (periarticular) and epidural (interlaminar), in the conservative treatment of LBP. This study used an open-label, randomized, controlled trial protocol. A group of 100 patients were enrolled in the study and randomly allocated into two comparative groups. Group A (n = 50) received the epidural (interlaminar) approach—2 ultrasound-guided injections as control intervention (each containing two doses of ACS—8 mL). Group B (n = 50) received the perineural (periarticular) approach—2 ultrasound-guided injections as experimental intervention at 7-day intervals (the same volume of ACS). Assessments consisted of an initial assessment (IA) and control assessments at 4 (T1), 12 (T2), and 24 (T3) weeks after the last intervention. Primary outcomes comprised Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Roland Morris Questionnaire (RMQ), and Euro Quality of Life—5 Dimensions–5 Levels (EQ-5D-5L): Index, Visual Analogue Scale (VAS), and Level Sum Score (LSS). Secondary outcomes included differences between groups in specific endpoints for the above-mentioned questionnaires. In conclusion, this study revealed that both perineural (periarticular) and epidural ACS injections tended to perform in a very similar way. Both routes of Orthokine application show significant improvement in the primary clinical parameters, such as pain and disability, and therefore, both methods can be considered equally effective in managing LBP due to LDDD. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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13 pages, 6437 KiB

Open AccessArticle

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats

by Zhen-Hua Xu, Zheng Niu, Yun Liu, Pei-Lin Liu, Xiao-Long Lin, Ling Zhang, Long Chen, Yu Song, Ren Sun and Hai-Long Zhang

Brain Sci. 2023, 13(4), 644; https://doi.org/10.3390/brainsci13040644 - 10 Apr 2023

Cited by 6 | Viewed by 2344

Abstract

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for [...] Read more.

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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Figure 1
The bone cancer pain model was successfully established by injecting Walker 256 tumor cells into the tibia of rats. (A) The mechanical pain threshold was significantly reduced from day 7 to day 21 in rats after surgery compared with the naïve group and sham group (*** p < 0.001 vs. sham group, n = 8, two-way ANOVA followed by Tukey’s multiple comparisons test). Pre, preoperative. (B) We compared the tibia of the operated side in the BCP group and the sham group. The arrow points demonstrated that tumor expansion had destroyed the bone in the BCP rat. (C) The tibial bone in the sham rats was intact, and the arrangement of the trabecular bone structure was orderly, as demonstrated by HE staining. Red blood cells, lymphocytes, and macrophages are present in large numbers in the bone marrow cavity. However, the morphological changes of trabecular bone were lost, and the bone cortex was thinned and even destroyed in the BCP rats, who also had a large number of tumor cells filling the bone marrow cavity at the posterior end of the rat tibia. The region circled by the white dashed line represents the invasion of cancer cells. Full article ">Figure 2
TET1 and TRPV4 were increased by qPCR and Western blotting at day 0, 3, 7, 14, and 21 in L4–6 DRG of BCP rats after tumor cell inoculation. (A) qPCR assay showed that TET1 mRNA increased with tumor progression (** p < 0.01, *** p < 0.001 vs. sham, n = 4, one-way ANOVA). (B) Compared with the sham group, TET2 mRNA has no significant difference at each time point. (C) qPCR assay showed that TRPV4 mRNA increased with tumor progression (** p < 0.01, *** p < 0.001 vs. sham, n = 4, one-way ANOVA). (D) Compared with the sham group, TET1 expression began to increase on the 3rd day after tumor cell inoculation and reached the highest level on the 7th day, and remained until the 21st day (*** p < 0.001 vs. sham, n = 4, one-way ANOVA). (E) TET2 expression was not significantly different from the sham group after tumor cell inoculation. (F) Compared with the sham group, TRPV4 expression began to increase on the 7th day after tumor cell inoculation (*** p < 0.001 vs. sham, n = 4, one-way ANOVA). Full article ">Figure 3
Immunofluorescence assay of TET1 in the L4–6 DRG of BCP rats. (A) The schematic diagram. (B) TET1-positive DRG cells (middle row) were mainly co-labeled as neurons (NeuN) but not with satellite glial cells (GS). TET1 was co-expressed in CGRP-positive and IB4-positive DRG neurons. (C) The proportion of TET1-positive cells in different cell types, n = 4. Full article ">Figure 4
Immunofluorescence assay of TRPV4 in the L4–6 DRG of BCP rats. (A) The schematic diagram. (B) TRPV4-positive DRG cells (middle row) were mainly co-labeled as neurons (NeuN) but not with satellite glial cells (GS). TRPV4 was co-expressed in CGRP-positive and IB4-positive DRG neurons. (C) The proportion of TRPV4-positive cells in different cell types, n = 4. Full article ">Figure 5
TET1 shuttled from the cytoplasm to the nucleus in BCP rats. (A,B) Compared with the sham group, the percentage of cells with TET1 nucleus entry was significantly increased in L4–6 DRG of BCP rats (*** p < 0.001 vs. sham, n = 4, two-tailed t-test). (C,D) No discernible difference in the proportion of cells with TET2 in the nucleus. Scale bar, 25 µm. Full article ">Figure 6
TET1 inhibitor Bob339 downregulated TRPV4 expression in L4−6 DRG of BCP rats. (A–C) The white arrows represent typical TRPV4−positive cells. After intrathecal injection of Bobcat339, there were significantly fewer TRPV4 positive cells in the L4−6 DRG of BCP rats than in the BCP + NS group (** p < 0.01, *** p < 0.001, n = 4, one−way ANOVA). Scale bar, 50 µm. (D,E) Compared with the BCP + NS, intrathecal injection of Bobcat339 significantly reduced TRPV4 expression in L4−6 DRG of BCP rats (*** p < 0.001, n = 4, one−way ANOVA). (F,G) Compared with the BCP + NS, intrathecal injection of Bobcat339 reduced TET1 expression in L4−6 DRG of BCP rats (*** p < 0.001, n = 4, one−way ANOVA). Full article ">Figure 7
TET1 inhibitor Bob339 or TRPV4 inhibitor HC067047 alleviated mechanical allodynia in BCP rats. (A) The schematic diagram. (B) Bobcat339 was intrathecally injected on the 8th day after tumor cell inoculation for 7 consecutive days. Compared with the BCP + NS group, the allodynia of BCP rats was significantly partially reversed (** p < 0.01 vs. sham, ## p < 0.01 vs. BCP + NS, n = 8, two−way ANOVA followed by Tukey’s multiple comparisons test). (C) HC067047 was intrathecally injected on the 8th day after tumor cell inoculation for 7 consecutive days. Compared with the BCP + NS group, the allodynia of BCP rats was significantly partially reversed (** p < 0.01 vs. sham, ## p < 0.01 vs. BCP + NS, n = 8, two−way ANOVA followed by Tukey’s multiple comparisons test). Full article ">

24 pages, 4666 KiB

Open AccessArticle

Pharmacological Modulation of the MIP-1 Family and Their Receptors Reduces Neuropathic Pain Symptoms and Influences Morphine Analgesia: Evidence from a Mouse Model

by Agata Ciechanowska, Katarzyna Pawlik, Katarzyna Ciapała and Joanna Mika

Brain Sci. 2023, 13(4), 579; https://doi.org/10.3390/brainsci13040579 - 29 Mar 2023

Cited by 5 | Viewed by 2302

Abstract

Neuropathic pain pathophysiology is not fully understood, but it was recently shown that MIP-1 family members (CCL3, CCL4, and CCL9) have strong pronociceptive properties. Our goal was to examine how pharmacological modulation of these chemokines and their receptors (CCR1 and CCR5) influence hypersensitivity [...] Read more.

Neuropathic pain pathophysiology is not fully understood, but it was recently shown that MIP-1 family members (CCL3, CCL4, and CCL9) have strong pronociceptive properties. Our goal was to examine how pharmacological modulation of these chemokines and their receptors (CCR1 and CCR5) influence hypersensitivity after nerve injury in Albino Swiss male mice. The spinal changes in the mRNA/protein levels of the abovementioned chemokines and their receptors were measured using RT-qPCR and ELISA/Western blot techniques in a mouse model of chronic constriction injury of the sciatic nerve. Behavioral studies were performed using the von Frey and cold plate tests after pharmacological treatment with neutralizing antibodies (nAbs) against chemokines or antagonists (CCR1-J113863, CCR5-TAK-220/AZD-5672) alone and in coadministration with morphine on Day 7, when the hypersensitivity was fully developed. Our results showed enhanced protein levels of CCL3 and CCL9 1 and 7 days after nerve injury. The single intrathecal administration of CCL3 or CCL9 nAb, J113863, TAK-220, or AZD-5672 diminished neuropathic pain symptoms and enhanced morphine analgesia. These findings highlight the important roles of CCL3 and CCL9 in neuropathic pain and additionally indicate that these chemokines play essential roles in opioid analgesia. The obtained results suggest CCR1 and CCR5 as new, interesting targets in neuropathy treatment. Full article

(This article belongs to the Special Issue Recent Advances in Pain Research)

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