title: Delayed Exercise Is Ineffective at Reversing Aberrant Nociceptive Afferent Plasticity or Neuropathic Pain After Spinal Cord Injury in Rats.
abstract: Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that correlates with sensory fiber sprouting. Recent data indicate that exercise initiated early after SCI prevents the development of allodynia and modulated nociceptive afferent plasticity. This study determined if delaying exercise intervention until pain is detected would similarly ameliorate established SCI-induced pain. Adult, female Sprague-Dawley rats with a C5 unilateral contusion were separated into SCI allodynic and SCI non-allodynic cohorts at 14 or 28 days postinjury when half of each group began exercising on automated running wheels. Allodynia, assessed by von Frey testing, was not ameliorated by exercise. Furthermore, rats that began exercise with no allodynia developed paw hypersensitivity within 2 weeks. At the initiation of exercise, the SCI Allodynia group displayed marked overlap of peptidergic and non-peptidergic nociceptive afferents in the C7 and L5 dorsal horn, while the SCI No Allodynia group had scant overlap. At the end of 5 weeks of exercise both the SCI Allodynia and SCI No Allodynia groups had extensive overlap of the 2 c-fiber types. Our findings show that exercise therapy initiated at early stages of allodynia is ineffective at attenuating neuropathic pain, but rather that it induces allodynia-aberrant afferent plasticity in previously pain-free rats. These data, combined with our previous results, suggest that there is a critical therapeutic window when exercise therapy may be effective at treating SCI-induced allodynia and that there are postinjury periods when exercise can be deleterious.
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA mdetloff@drexelmed.edu.
authors.forename: Megan Ryan
authors.initials: MR
authors.lastname: Detloff
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Quiros-Molina
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Javia
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Lekhaj
authors.initials: L
authors.lastname: Daggubati
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Nehlsen
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Naqvi
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Vinu
authors.initials: V
authors.lastname: Ninan
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Kirsten N
authors.initials: KN
authors.lastname: Vannix
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Mary-Katharine
authors.initials: MK
authors.lastname: McMullen
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Sheena
authors.initials: S
authors.lastname: Amin
authors.affiliation: University of Texas at Dallas, Richardson, TX, USA.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Ganzer
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Houlé
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D007839:Functional Laterality; D006023:Glycoproteins / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology; D037102:Lectins / Q000378:metabolism; D009043:Motor Activity; D009437:Neuralgia / Q000209:etiology* / Q000473:pathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D010147:Pain Measurement; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D053675:Versicans
chemical_list: D006023:Glycoproteins; D037102:Lectins; C508324:Vcan protein, rat; D053675:Versicans; D002772:Cholera Toxin; D015740:Calcitonin Gene-Related Peptide
keywords: central pain; mechanical allodynia; neuroplasticity; nociceptor; rehabilitation; spinal cord injury