Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat.
Our laboratory has previously shown that glial activation and increased proinflammatory cytokine expression are observed in the rat spinal cord following peripheral nerve injuries that result in neuropathic pain behaviors. In the present study, we sought to determine whether acute peripheral inflammation induces changes in central glial and cytokine (Interleukin-1beta) expression similar to those seen following peripheral spinal nerve transection. Two models of peripheral inflammation were used in this study: formalin (5% solution) or zymosan (25 mg/ml) injected subcutaneously into the plantar portion of the left hind paw of male Holtzman-strain Sprague-Dawley rats. The rats were euthanized at 1 h, 6 h, and 1, 3, 7 days post-injection (n=4 or 5/group/time point). As expected, the animals treated with formalin showed a spontaneous pain response and mechanical allodynia that persisted for approximately 60 min following injection. The animals treated with zymosan exhibited mild spontaneous pain responses during the first hour and mechanical allodynia at 6 h and 1 day following injection. Immunohistochemistry for glial activation and cytokine expression was performed on L4-L5 spinal levels in all rats. Spinal sections from both formalin and zymosan treated animals exhibited microglial and astrocytic activation and increased Interleukin-1beta immunoreactivity at 1 and 6 h, respectively. Spinal glial activation and upregulation of Interleukin-1beta appear to parallel the development and maintenance of zymosan and formalin-induced mechanical allodynia. These findings support a unifying theory that glial activation and cytokine expression have a similar, if not related, role in producing hyperalgesia following either peripheral inflammation or peripheral nerve injury.
Sweitzer
S M
SM
Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA. sarah.sweitzer@dartmouth.edu
Colburn
R W
RW
Rutkowski
M
M
DeLeo
J A
JA
D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis*; D008297:Male; D017628:Microglia / Q000187:drug effects; D009443:Neuritis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000503:physiopathology*; D013314:Stress, Mechanical; D015054:Zymosan
D007375:Interleukin-1; D015054:Zymosan