A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac

Atzeni, Fabiola; Masala, Ignazio Francesco; Sarzi‐Puttini, Piercarlo

doi:10.1007/s40122-018-0100-2

Cited by 42 publications

(29 citation statements)

References 98 publications

(113 reference statements)

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“…The MIA injection causes immediate onset of mechanical hyperalgesia (8,9), altered weight bearing (10), and reduction in mobility (11), all of which are associated with the early inflammatory phase (days 0-7) of OA. This is then followed by a more persistent allodynia, typical in late-phase OA (days [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Pain-like behaviors increase in a dose-dependent manner, with late-phase hypersensitivity typically observed with higher doses of MIA (12).…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Mechanical Joint Loading as an Alternative Model for Osteoarthritic Pain

Heegde

Luiz

Santana-Varela

et al. 2019

Arthritis & Rheumatology

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Objective Mechanisms responsible for osteoarthritic (OA) pain remain poorly understood, and current analgesic therapies are often insufficient. This study was undertaken to characterize and pharmacologically test the pain phenotype of a noninvasive mechanical joint loading model of OA, thus providing an alternative murine model for OA pain. Methods The right knees of 12‐week‐old male C57BL/6 mice were loaded at 9N or 11N (40 cycles, 3 times per week for 2 weeks). Behavioral measurements of limb disuse and mechanical and thermal hypersensitivity were acquired before mechanical joint loading and monitored for 6 weeks postloading. The severity of articular cartilage lesions was determined postmortem with the Osteoarthritis Research Society International scoring system. To assess efficacy of various treatments for pain, 9N‐loaded mice were treated for 4 weeks with diclofenac (10 mg/kg), gabapentin (100 mg/kg), or anti–nerve growth factor (anti‐NGF) (3 mg/kg). Results Mechanical hypersensitivity and weight bearing worsened significantly in 9N‐loaded mice (n = 8) and 11N‐loaded mice (n = 8) 2 weeks postloading, compared to baseline values and nonloaded controls. Maximum OA scores of ipsilateral knees confirmed increased cartilage lesions in 9N‐loaded mice (mean ± SEM 2.8 ± 0.2; P < 0.001) and 11N‐loaded mice (5.3 ± 0.3; P < 0.001), compared to nonloaded controls (1.0 ± 0.0). Gabapentin and diclofenac restored pain behaviors to baseline values after 2 weeks of daily treatment, and gabapentin was more effective than diclofenac. A single injection of anti‐NGF alleviated nociception 2 days after treatment and remained effective for 2 weeks, with a second dose inducing stronger and more prolonged analgesia. Conclusion Our findings show that mechanical joint loading induces OA lesions in mice and a robust pain phenotype that can be reversed using analgesics known to alleviate OA pain in patients. This establishes the use of mechanical joint loading as an alternative model for the study of OA pain.

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Section: Introductionmentioning

confidence: 99%

Noninvasive Mechanical Joint Loading as an Alternative Model for Osteoarthritic Pain

Heegde

Luiz

Santana-Varela

et al. 2019

Arthritis & Rheumatology

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“…NSAIDs such as ibuprofen, ketoprofen, salicylate, naproxen and diclofenac have been used for pain management along with physical therapy [ 11 , 15 ]. Diclofenac has shown the most efficacy, as COX-1/2 inhibitors lead to the downregulation of prostaglandin-2 and associated inflammatory cytokines such as us IL-1β, TNF α, along with MMP 13, a disintegrin and metalloproteinase with thrombospondin-1 domains 4 and 5 [ 13 , 14 , 34 , 41 ]. Systemic application of long-term use NSAIDs can cause severe damage to the kidney, liver and gastrointestinal complications, while only providing short-term pain relief.…”

Section: Discussionmentioning

confidence: 99%

“…The topical application of NSAIDs reduces the systemic risks but has reduced efficacy due to limited penetration through the skin [ 12 ]. Diclofenac is one of the most common NSAIDs used [ 13 , 14 ]. It inhibits COX-1 and -2, the underlying expression of prostaglandin-2 and thromboxane synthesis approximately 3–1000× more than other NSAIDs [ 15 ].…”

mentioning

confidence: 99%

“…It inhibits COX-1 and -2, the underlying expression of prostaglandin-2 and thromboxane synthesis approximately 3–1000× more than other NSAIDs [ 15 ]. Furthermore, inhibition of COX-1 and COX-2 downregulate pain sensitization through the L-arginine/nitric oxide/cyclic guanosine monophosphate pathway [ 13 , 14 ]. Recent meta-analyses have shown that diclofenac is more effective, relative to other NSAIDs, such as ketoprofen, ibuprofen and piroxicam [ 9 , 15 , 16 ].…”

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confidence: 99%

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Sustained Acoustic medicine; Sonophoresis for Nonsteroidal anti-inflammatory Drug Delivery in Arthritis

et al. 2020

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Background: Arthritis pain is primarily managed by nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac. Topical diclofenac gel is limited in efficacy due to its limited penetration through the skin. This study investigates the use of a multihour, wearable, localized, sonophoresis transdermal drug delivery device for the penetration enhancement of diclofenac through the skin. Materials & methods: A commercially available, sustained acoustic medicine (sam®) ultrasound device providing 4 h, 1.3 W, 132 mW/cm2, 3 MHz ultrasound treatment was evaluated for increasing the drug delivery of diclofenac gel through a human skin model and was compared with standard of care topical control diclofenac gel. Results: Sonophoresis of the diclofenac gel for 4 h increases diclofenac delivery by 3.8× (p < 0.01), and penetration by 32% (p < 0.01). Conclusion: Sustained acoustic medicine can be used as a transdermal drug-delivery device for nonsteroidal anti-inflammatory drugs.

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“…CFA is often used in the induction of various chronic inflammatory pain models. The study of peripheral and central mechanisms of inflammatory pain has been focused by the international research (Xu et al, 2010; Atzeni et al, 2018; Rosas et al, 2018). Numerous studies have shown that many peripheral and central nervous structures and a variety of chemicals are involved in the formation and regulation of inflammatory pain (Vane and Botting, 1995).…”

Section: Introductionmentioning

confidence: 99%

Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling

et al. 2019

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Background Zanthoxylum nitidum (Roxb.) DC. , also named Liang Mianzhen (LMZ), one kind of Chinese herb characterized with anti-inflammatory and relieving pain potency, which is widely used to treat injuries, rheumatism, arthralgia, stomach pain and so on in China. But its mechanism related to the anti-hyperalgesic has not been reported. The aim of this study was to investigate the analgesic activity of Liang Mianzhen on mice with Complete Freund adjuvant (CFA)-induced chronic inflammatory pain. Meanwhile, the peripheral and central mechanisms of analgesic effect of Liang Mianzhen were further examined via observing the effects of Liang Mianzhen on the signal pathway associated with inflammatory induced hyperalgesia. Methods The inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After 1 day of CFA injection, the mice were treated with LMZ (100 mg/kg) for seven consecutive days, and the behavioral tests were measured after the daily intragastric administration of LMZ. The morphological changes on inflamed paw sections were determined by hematoxylin eosin (HE) staining. Changes in the mRNA expression levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor κB p65 (NF-κBp65) were measured on day seven after CFA injection by using real-time quantitative PCR analysis and enzyme linked immunosorbent assay (ELISA) method, respectively. Moreover, immunohistochemistry and western blotting were used to detect extracellular regulated protein kinases 1/2 (ERK1/2) and NF-κB signal pathway activation. Results The extract of LMZ (100 mg/kg) showed a significant anti-inflammatory and analgesic effect in the mice model. The paw edema volume was significantly reduced after the administration of LMZ compared to CFA group, as well as the paw tissues inflammatory damage was relived and the numbers of neutrophils in mice was reduced significantly. The CFA-induced mechanical threshold and thermal hyperalgesia value were significant improved with LMZ treatment at day three to day seven. We also found the mRNA levels of TNF-α, IL-1β, IL-6 and NF-κBp65 were down-regulate after 7 days from the LMZ treatment compared to CFA group. Meanwhile, LMZ significantly suppressed over-expression of the phosphorylation of ERK1/2 and NF-κBp65 in peripheral and central. Conclusion The present study suggests that the extract of LMZ attenuates CFA-induced inflammatory pain by suppressing the ERK1/2 and NF-κB signaling pathway at both peripheral and central level.

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A Review of Chronic Musculoskeletal Pain: Central and Peripheral Effects of Diclofenac

Cited by 42 publications

References 98 publications

Noninvasive Mechanical Joint Loading as an Alternative Model for Osteoarthritic Pain

Noninvasive Mechanical Joint Loading as an Alternative Model for Osteoarthritic Pain

Sustained Acoustic medicine; Sonophoresis for Nonsteroidal anti-inflammatory Drug Delivery in Arthritis

Analgesic Effect of Zanthoxylum nitidum Extract in Inflammatory Pain Models Through Targeting of ERK and NF-κB Signaling

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