Referred pain frequently occurs in musculoskeletal pain disorders. The differential role of peripheral (nociceptive drive) and central (pain processing) domains associated with referred pain was investigated. Utilizing TMJ IMPACT Project data, 293 participants were classified into 2 groups: referred pain (n=118) and local pain (n=175). Each domain of nociceptive drive and central processing was comprised of 7 observed variables as predictors based on face validity. Latent variables for each domain were constructed using confirmatory factor analysis (CFA). Univariate associations of predictors and multivariate associations of latent variables were tested with logistic models. Referred pain, compared to local pain, was associated with each of 6 nociceptive drive predictors (odds ratios (ORs) ranging 1.03-1.41), and 4 central processing predictors (ORs ranging 1.03-1.8); confidence limits (95%) were appropriately narrow. The latent variable model indicated that nociceptive drive was comprised of non-specific orofacial symptoms, pain-free opening, mobility assessment-based hyperalgesia, pain sensitivity (trigeminal), joint sounds, and painful body-manikin sites above the neck. Central processing was comprised of non-specific body symptoms, perceived stress, pain-catastrophizing, and painful body-manikin sites below the neck. The CFA model fit was marginally acceptable. Using latent variables, referred pain was univariately associated with nociceptive drive (OR=2.5; 95%CL=1.8-3.3) and central processing (OR=1.7; 95%CL=1.3-2.2). In the multivariate model, nociceptive drive remained significant (OR=2.4; 95%CL=1.7-3.3), whereas central processing did not. While nociceptive drive and central mechanisms are distinct but overlapping contributors based on multiple indicators, the processes associated with the nociceptive drive indicators may be primary for activation of pain referral. PERSPECTIVE: Both nociceptive drive and central pain processing are involved with the report of referred pain. Using a latent variable model, nociceptive drive indicators reflecting masticatory system sensory changes dominate and point to the need for a broad, peripherally oriented therapeutic approach to restore normal function of the masticatory system. Keywords: Myofascial pain; central pain mechanism; nociceptive drive; referred pain.