Pain in both peripheral and axial joints is a major symptom in patients with psoriaticarthritis (PsA) and axial spondyloarthritis (axSpA). Emerging evidence demonstrates pain mechanisms,beyond those related to inflammation or joint damage, based on aberrant processing of nociceptivestimuli peripherally as well as centrally. The Janus kinase/signal transducers and activators of transcrip-tion (JAK-STAT) signaling pathway has been implicated in the processing of pain beyond its role inmediating inflammation and inhibitors of this pathway approved for the treatment of axSpA and PsAhave been shown to alleviate a broad array of pain outcomes in both axial and peripheral joints.Areas covered: We review recent definitions and standardization of the nomenclature for categorizingchronic pain according to causality, assessment tools to evaluate nociplastic pain, the pathophysiologic roleof JAK-STAT signaling in nociplastic pain, evidence for the presence of nociplastic pain in axSpA and PsA,and the impact of JAK inhibitors (JAKi) on pain outcomes in clinical trials (PubMed: 01/01/2019-04/01-2024).Expert opinion: Nociplastic pain assessment has been confined almost entirely to the use of a limitednumber of questionnaires in cross-sectional studies of these diseases. Though effective for alleviatingpain, it is unclear if JAKi specifically impact nociplastic pain.ARTICLE HISTORYReceived 20 May 2024Accepted 30 August 2024KEYWORDSAnkylosing spondylitis; axialspondyloarthritis; nociplasticpain; janus kinases; psoriaticarthritis1. IntroductionPain is a key symptom of the inflammatory arthritis that may affectaxial and peripheral joints in patients with axSpA and PsA. Recentavailability of bDMARD and targeted synthetic DMARD (tsDMARD)agents targeting cytokines implicated in inflammation has led toa significantly beneficial impact on pain as well as other symptomsrelated to joint inflammation. However, remission of pain aftersuch treatment occurs in only 20–25% of patients, irrespective ofthe DMARD that is used. Moreover, evaluation of the severity ofand changes in inflammation using objective measures of inflam-mation, such as serum C-reactive protein (CRP) and magneticresonance imaging (MRI) parameters of joint inflammation, hasdemonstrated only limited correlation with assessments of painseverity and change with treatment, this being limited to patientswith short symptom duration and dissipating over time.Conversely, recent work in axSpA has demonstrated beneficialeffects of a specific bDMARD on pain in the apparent absence ofany objective features of inflammation [1].The recent introduction of JAKi for the treatment of PsA andaxSpA has further put the spotlight on our understanding ofmechanisms accounting for pain in these conditions because ofobservations demonstrating a rapid onset of significant pain reliefin clinical trials [2,3]. This has coincided with recent studies inanimal models suggesting a role for JAK-STAT signaling, andcytokines modulated by JAK signaling pathways, in peripheraland central processing of afferent pain signals [4,5]. There is alsoincreasing awareness that abnormalities of central and peripheralpain processing pathways, unrelated to abnormalities of neural ornon-neural tissues such as joints, may be important contributorsto the perception of pain in patients with axSpA and PsA.This manuscript aims to review the recent literature thatfocuses on a consensus-based mechanistic framework fordefining different categories of pain, outcome tools for theassessment of these different categories of pain, evidence forthe presence of pain in axSpA and PsA that may be unrelatedto inflammation or joint damage, the evidence supportinga role for JAK-STAT signaling in non-inflammatory pain, andwhat is known from clinical trials about the impact of treat-ment with JAKi on pain that may be unrelated to anti-inflammatory effects. The review will focus particularly onnociplastic pain, which is an emerging area of considerableinterest to clinicians because of its prevalence in patients withaxSpA and PsA, and the possibility that JAKi could havediverse mechanistic effects in ameliorating pain.2. Nomenclature of chronic pain and relevantoutcome tools2.1. Pain definitions and the international associationfor the study of pain frameworkIn 2020, the International Association for the Study of Pain(IASP) updated the general definition of pain for the first timeCONTACT Walter P. Maksymowych walter.maksymowych@ualberta.ca Department of Medicine, University of Alberta, 568 Heritage Medical ResearchBuilding, Edmonton, Alberta T6R 2G8, CanadaEXPERT REVIEW OF CLINICAL IMMUNOLOGY2025, VOL. 21, NO. 2, 137–152https://doi.org/10.1080/1744666X.2024.2400294© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.