Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia
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AutorMontilla-García, Ángeles; Tejada, Miguel Ángel; Perrazzoli, Gloria; Entrena Fernández, José Manuel; Portillo-Salido, Enrique; Fernández-Segura, Eduardo; Cañizares García, Francisco Javier; Cobos del Moral, Enrique José
Grip strengthFunctional disabilityAnimal modelJoint painPeriarticular inflammationAnalgesia
Montilla-García, A.; et al. Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia. Neuropharmacology, 125: 231-242 (2017). [http://hdl.handle.net/10481/47543]
PatrocinadorThis study was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2013-47481P), the Junta de Andalucía (grant CTS 109), and funding from Esteve and the European Regional Development Fund (FEDER).
Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1–8 mg/kg) and tramadol (10–80 mg/kg) induced a better recovery of grip strength than acetaminophen (40–320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10–80 mg/kg) or celecoxib (40–160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside.