Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (<i>TACR</i>1) gene

Warner, Sophie C; Walsh, David A.; Laslett, Laura L; Maciewicz, Rose A.; Soni, Anushka; Hart, Deborah; Zhang, Weiya; Muir, Kenneth; Dennison, Elaine; Leaverton, Paul E.; Rampersaud, Evadnie; Cooper, Cyrus; Spector, Tim D.; Cicuttini, Flavia Maria; Arden, N K; Jones, Graeme; Doherty, Michael; Valdes, Ana M.

doi:10.1002/ejp.1027

Cited by 28 publications

(21 citation statements)

References 31 publications

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“…central pain pathways and genetic factors. 7,33,35 This study also shows that the functional status of the shoulder, evaluated according to the CS-Score items "mobility" and "strength" are clearly associated with the severity of the radiographic articular changes. This might be explained by the fact that a decreased joint volume, a tight capsule, osteophytes and the deformation of the articular surface may cause a mechanical restriction of the joint motion as well as a reduced ability to raise and hold a speci c weight in a given position.…”

Section: Discussionsupporting

confidence: 60%

Patients Age is a Critical Factor in Determining the Severity of Osteoarthritis of the Shoulder

Märtens

Maerz

Bertrand

et al. 2020

Preprint

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Background: Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the aging population. The correlation of radiographic OA severity, disability and pain is variable and inconsistent for the different joints. This study aims to elucidate the relationship between histological and radiological signs of shoulder OA with pain sensation and functional impairment to potentially adapt the recommendation for surgical treatment for primary total shoulder arthroplasty (TSA). Methods: Forty-four patient with shoulder OA undergoing a TSA using an anatomic stemless implant were included in this study. The radiological OA severity was scored preoperatively on true ap X-rays according to the Kellgren-Lawrence-Score (KL-Score). The histological OA severity was determined according to the OARSI-Score using bone-cartilage sections from loaded areas of the humeral head. Pain was quantified with the Visual Analog Scale (VAS). The functional status was assessed by the items “mobility” and “strength” out of the Constant-Murley-Score (CS-Score). Results: There was no correlation between radiographic and histological severity in shoulder OA. However, a correlation between age and the severity of radiological changes was observed. Further, pain did not correlate with histological or radiological scores, whereas it correlated with age. The functional shoulder status (mobility, strength) correlated with the severity of radiological changes, but not with the histologic scoring. Conclusion: This study shows that increased age is the main determinant of radiological changes in shoulder OA, as well as pain. Therefore, age and pain sensation should be considered as important parameters for the recommendation for TSA.

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Section: Discussionsupporting

confidence: 60%

Patients Age is a Critical Factor in Determining the Severity of Osteoarthritis of the Shoulder

Märtens

Maerz

Bertrand

et al. 2020

Preprint

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“…Second, SF SP has been reported in KOA patients [22], and the level of SP has been correlated with pain relief after treatment with medication [46]. The SP receptor (TACR1) gene has also been correlated with pain in KOA [47], though to date, no study has reported a link between SP and pain intensity. Our study showed no correlation between SF SP and OA pain.…”

Section: Discussionmentioning

confidence: 99%

Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

Liu

et al. 2020

BMC Musculoskelet Disord

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Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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“…At this time, neurogenic SP could act on NK1 in the cartilage cell membrane in a paracrine manner, thus accelerating cartilage degeneration. In animal models and human studies of OA, SP, and NK receptors have been linked to joint pain, inflammation, and injury (77,78).…”

Section: Pathological Effects-osteoarthritismentioning

confidence: 99%

The Role of Substance P in the Regulation of Bone and Cartilage Metabolic Activity

Lin

et al. 2020

Front. Endocrinol.

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Substance P (SP) is a neuropeptide that is released from sensory nerve endings and is widely present in nerve fibers. It acts on bones and related tissues by binding to receptors, thereby regulating bone metabolism, cartilage metabolism, and fracture healing. SP has attracted widespread attention as a signaling substance that can be recognized by both the immune system and the nervous system. Previous studies have shown that bone and chondrocytes can synthesize and secrete sensory neuropeptides and express their receptors, and can promote proliferation, differentiation, apoptosis, matrix synthesis, and the degradation of target cells through autocrine/paracrine modes. In this paper, we review the research progress made in this field in recent years in order to provide a reference for further understanding the regulatory mechanism of bone and cartilage physiology and pathological metabolism.

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Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene

Abstract: This study contributes to the knowledge of the genetics of painful osteoarthritis, a condition which affects millions of individuals worldwide. Specifically, a contribution from the TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.

Cited by 28 publications

References 31 publications

Patients Age is a Critical Factor in Determining the Severity of Osteoarthritis of the Shoulder

Patients Age is a Critical Factor in Determining the Severity of Osteoarthritis of the Shoulder

Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

The Role of Substance P in the Regulation of Bone and Cartilage Metabolic Activity

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