Longitudinal case-controlled animal study. To investigate putative cellular mechanisms to explain structural changes in muscle and adipose and connective tissues of the back muscles after intervertebral disc (IVD) injury. Structural back muscle changes are ubiquitous with back pain/injury and considered relevant for outcome, but their exact nature, time course, and cellular mechanisms remain elusive. We used an animal model that produces phenotypic back muscle changes after IVD injury to study these issues at the cellular/molecular level. Multifidus muscle was harvested from both sides of the spine at L1–L2 and L3–L4 IVDs in 27 castrated male sheep at 3 (n = 10) or 6 (n = 17) months after a surgical anterolateral IVD injury at both levels. Ten control sheep underwent no surgery (3 mo, n = 4; 6 mo, n = 6). Tissue was harvested at L4 for histological analysis of cross-sectional area of muscle and adipose and connective tissue (whole muscle), plus immunohistochemistry to identify proportion and cross-sectional area of individual muscle fiber types in the deepest fascicle. Quantitative polymerase chain reaction measured gene expression of typical cytokines/signaling molecules at L2. Contrary to predictions, there was no multifidus muscle atrophy (whole muscle or individual fiber). There was increased adipose and connective tissue (fibrotic proliferation) cross-sectional area and slow-to-fast muscle fiber transition at 6 but not 3 months. Within the multifidus muscle, increases in the expression of several cytokines (tumor necrosis factor α and interleukin-1β) and molecules that signal trophic/atrophic processes for the 3 tissue types (e.g., growth factor pathway [IGF-1, PI3k, Akt1, mTOR], potent tissue modifiers [calcineurin, PCG-1α, and myostatin]) were present. This study provides cellular evidence that refutes the presence of multifidus muscle atrophy accompanying IVD degeneration at this intermediate time point. Instead, adipose/connective tissue increased in parallel with the expression of the genes that provide putative mechanisms for multifidus structural remodeling. This provides novel targets for pharmacological and physical interventions. Level of Evidence: N/A

Objectives: Improvements in pain management might be achieved by matching treatment to underlying mechanisms for pain persistence. Many authors argue for a mechanism-based classification of pain, but the field is challenged by the wide variation in the proposed terminology, definitions, and typical characteristics. This study aimed to (1) systematically review mechanism-based classifications of pain experienced in the musculoskeletal system; (2) synthesize and thematically analyze classifications, using the International Association for the Study of Pain categories of nociceptive, neuropathic, and nociplastic as an initial foundation; and (3) identify convergence and divergence between categories, terminology, and descriptions of each mechanism-based pain classification.Materials and Methods: Databases were searched for papers that discussed a mechanism-based classification of pain experienced in the musculoskeletal system. Terminology, definitions, underlying neurobiology/pathophysiology, aggravating/easing factors/response to treatment, and pain characteristics were extracted and synthesized on the basis of thematic analysis.Results: From 224 papers, 174 terms referred to pain mechanisms categories. Data synthesis agreed with the broad classification on the basis of ongoing nociceptive input, neuropathic mechanisms, and nociplastic mechanisms (eg, central sensitization). “Mixed,” “other,” and the disputed categories of “sympathetic” and “psychogenic” pain were also identified. Thematic analysis revealed convergence and divergence of opinion on the definitions, underlying neurobiology, and characteristics.Discussion: Some pain categories were defined consistently, and despite the extensive efforts to develop global consensus on pain definitions, disagreement still exists on how each could be defined, subdivided, and their characteristic features that could aid differentiation. These data form a foundation for reaching consensus on classification.

Study Design. Longitudinal case-controlled animal study. Objective. To investigate the effect of an intervertebral disc (IVD) lesion on the proportion of slow, fast, and intermediate muscle fiber types in the multifidus muscle in sheep, and whether muscle fiber changes were paralleled by local gene expression of the proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1-β. Summary of Background Data. Structure and behavior of the multifidus muscle change in acute and chronic back pain, but the mechanisms are surprisingly poorly understood and the link between structure and behavior is tenuous. Although changes in muscle fiber types have the potential to unify the observations, the effect of injury on muscle fiber distribution has not been adequately tested, and understanding of possible mechanisms is limited. Methods. The L1–L2, L3–L4, and L5–L6 IVDs of 11 castrated male sheep received anterolateral lesions. Six control sheep underwent no surgical procedures. Multifidus muscle tissue was harvested at L4 for muscle fiber analysis using immunohistochemistry and L2 for cytokine analysis with polymerase chain reaction for local gene expression of TNF-α and interleukin-1β. Results. The proportion of slow muscle fibers in multifidus was significantly less in the lesioned animals both ipsilateral and contralateral to the IVD lesion. The greatest reduction in slow fibers was in the deep medial muscle region. A greater prevalence of intermediate fibers on the uninjured side implies a delayed fiber-type transformation on that side. TNF-α gene expression in multifidus was greater on both sides in the lesion animals than in the muscle of control animals. Interleukin-1β was increased only on the injured side. Conclusion. These data provide evidence of muscle fiber changes after induction of an IVD lesion and a parallel increase in TNF-α expression. Proinflammatory cytokine changes provide a novel mechanism to explain behavioral and structural changes in multifidus. Level of Evidence: N/A