Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task

Abstract

BackgroundSystemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.MethodsExperimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.ResultsTRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.ConclusionsThese results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-017-0354-3) contains supplementary material, which is available to authorized users.

Decreased grip strength, muscle pain, and atrophy occur in rats following long‐term exposure to excessive repetitive motion

“…This interpretation is consistent with those of Xin et al . , who reported that inflammation and pain in a WMSD model (albeit using a different force magnitude from that in our study, i.e., a difference in intensity in task performance) do not involve the same pathway. Elliott et al .…”

“…In addition, upregulation of NGF and GDNF in EDL muscle was essential to mechanical hyperalgesia in an animal model of DOMS, caused by repeated lengthening contractions . DOMS after intense acute swimming, leading to upregulated TNF‐α in soleus muscle, was required for mechanical hyperalgesia . Accordingly, we measured NGF, GDNF, and TNF‐α levels in FDS muscle to investigate the mechanism of muscle mechanical hyperalgesia caused by continuing repetitive reaching and grasping tasks.…”

“…Recently, Xin et al . studied skin pain, often assessed with a von Frey hair test, in a WMSD model. However, according to Nasu et al .…”

Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse

“…An early treatment timepoint was chosen to tease out whether CCN2 plays a key role in the progression of fibrosis in this chronic overuse model, or if persistent mechanical loading alone increases collagen production through TGFβ1 signaling pathways independent of CCN2 . As indicated above, increased muscle levels of CCN2 and TGFβ1 are already present in 0‐week HRHF rats, yet, indices of central sensitization (i.e., spinal cord changes associated with chronic pain) are not detectable until HRHF week 6 . This earlier timepoint allowed us to avoid central nervous system changes that would confound interpretation of behavioral findings.…”

Blocking CTGF/CCN2 reduces established skeletal muscle fibrosis in a rat model of overuse injury

“…Custom‐designed operant behavioral chambers were used in which rats performed an operant reaching and lever pulling task, as previously described 32‐34 . As an overview, task rats were shaped for 6 weeks to learn a reaching and lever‐pulling task at high force loads.…”