Periarticular Neurogenic Inflammation as a Candidate Early Mechanism in Hand Osteoarthritis

Hand osteoarthritis (OA) is usually classified as a non-inflammatory or low-grade inflammatory disorder, yet many patients report pain, tenderness and periarticular puffiness long before nodal or radiographic change appears. This Hypothesis and Theory preprint proposes that in a defined subset of early hand OA - joints in which standardized, scored imaging finds no significant synovitis - the dominant early process is neurogenic inflammation driven by somatic nociceptors rather than by innate-immune pattern recognition. Two sensing axes are described: innate-immune-dominant (Type C) and nociceptor-dominant (Type N) inflammation, framed as the relative dominance of two coexisting processes rather than mutually exclusive categories. The immunological mechanism is set out explicitly: antidromic axon-reflex release of substance P acting on mast cells through MRGPRX2 and on venular endothelium through NK1R, alongside CGRP acting on arteriolar smooth muscle through CLR/RAMP1, generating cytokine and chemokine feedback that re-sensitizes the nociceptor. Operational criteria are proposed that make the subset identifiable, every evidence domain is graded for directness with respect to human hand OA, and the unsupported links in the proposed chain are stated plainly. Eight falsifiable predictions are given, each paired with the observation that would refute it. De-identified bedside photographs are included as original illustrative clinical observations, not as an analysed dataset.