Chronic at-level thermal hyperalgesia following rat cervical contusion spinal cord injury is accompanied by neuronal and astrocyte activation and loss of the astrocyte glutamate transporter, GLT1, in superficial dorsal horn.
Neuropathic pain is a form of pathological nociception that occurs in a significant portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. While many peripheral and central mechanisms have been implicated in neuropathic pain, central sensitization of dorsal horn spinothalamic tract (STT) neurons is a major underlying substrate. Furthermore, dysregulation of extracellular glutamate homeostasis and chronic astrocyte activation play important underlying roles in persistent hyperexcitability of these superficial dorsal horn neurons. To date, central sensitization and astrocyte changes have not been characterized in cervical SCI-induced neuropathic pain models, despite the fact that a major portion of SCI patients suffer contusion trauma to cervical spinal cord. In this study, we have characterized 2 rat models of unilateral cervical contusion SCI that behaviorally result in chronic persistence of thermal hyperalgesia in the ipsilateral forepaw. In addition, we find that STT neurons are chronically activated in both models when compared to laminectomy-only uninjured rats. Finally, persistent astrocyte activation and significantly reduced expression of the major CNS glutamate transporter, GLT1, in superficial dorsal horn astrocytes are associated with both excitability changes in STT neurons and the neuropathic pain behavioral phenotype. In conclusion, we have characterized clinically-relevant rodent models of cervical contusion-induced neuropathic pain that result in chronic activation of both STT neurons and astrocytes, as well as compromise in astrocyte glutamate transporter expression. These models can be used as important tools to further study mechanisms underlying neuropathic pain post-SCI and to test potential therapeutic interventions.
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University Medical College, 900 Walnut Street, JHN 469, Philadelphia, PA 19107, USA.
Rajarshi
R
Putatunda
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University Medical College, 900 Walnut Street, JHN 469, Philadelphia, PA 19107, USA.
Tamara J
TJ
Hala
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University Medical College, 900 Walnut Street, JHN 469, Philadelphia, PA 19107, USA.
Jeannie
J
Chin
Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University Medical College, 900 Walnut Street, JHN 469, Philadelphia, PA 19107, USA. Electronic address: Angelo.Lepore@jefferson.edu.
Angelo C
AC
Lepore
D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D015153:Blotting, Western; D002574:Cervical Vertebrae; D002908:Chronic Disease; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005260:Female; D005552:Forelimb; D007839:Functional Laterality; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
D027342:Excitatory Amino Acid Transporter 2; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; C493395:Slc1a2 protein, rat
Astrocyte; Cervical; Contusion; GLT1; Glutamate transporter; Hyperalgesia; Hyperexcitability; Neuropathic pain; Spinal cord injury