Therapeutic Soreness in Manual Therapy for Chronic Neck Pain: A Triphasic Model of Descending Pain Modulation.

Chronic neck pain (CNP) is a complex condition shaped by both peripheral tissue dysfunction and central nociplastic changes, including dysregulated endogenous pain modulation. Manual therapy (MT) is a guideline-endorsed intervention, but its mechanism of action remains debated. Moving beyond purely biomechanical accounts, we propose, as a working hypothesis rather than an established finding, that MT's clinical effects may be substantially mediated by neurophysiological modulation, particularly recruitment of descending inhibitory pathways. We synthesize contemporary evidence to propose that the "therapeutic soreness" some patients report during MT may indicate an afferent stimulus intensity sufficient to engage deep somatic Aδ and C-fiber input to the descending pain-modulatory system, centered on the Periaqueductal Gray (PAG)-Rostral Ventromedial Medulla (RVM) loop. We also review animal pharmacology implicating Locus Coeruleus (LC) noradrenergic and endocannabinoid signaling in shifting RVM output toward antinociceptive OFF-cell dominance; whether this specific chain operates during manual therapy in humans has not been directly tested. We propose a conceptual, non-linear triphasic (Zone 1-2-3) dose-response framework as a hypothesis-generating tool, not a validated protocol. Subthreshold loading (Zone 1) is proposed to produce local tissue effects without engaging robust central modulation. An intermediate intensity (Zone 2), clinically associated with tolerable "therapeutic soreness", is hypothesized to engage descending inhibition through mechanisms that resemble, but are not equivalent to, Conditioned Pain Modulation (CPM-like effects). Loading beyond this window (Zone 3) is proposed to shift the balance toward central facilitation, potentially reinforcing rather than resolving the pain-tension cycle. This framework offers a testable, neurobiologically motivated rationale for individualizing MT dosing, particularly in sensitized phenotypes where the therapeutic window may be narrowed. It requires empirical validation, including objective sensorimotor and neuroimmune biomarkers, before it can inform clinical decision-making.