Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury

Pain. 2011 Apr;152(4):888-95. doi: 10.1016/j.pain.2011.01.004. Epub 2011 Feb 5.


Sensitization of primary afferent neurons is one of the most important components of pain hypersensitivity after tissue injury. Insulin-like growth factor 1 (IGF-1), involved in wound repair in injured tissue, also plays an important role in maintaining neuronal function. In the present study, we investigated the effect of tissue IGF-1 on nociceptive sensitivity of primary afferent neurons. Local administration of IGF-1 induced thermal and mechanical pain hypersensitivity in a dose-dependent manner, and was attenuated by IGF-1 receptor (IGF1R) inhibition. Tissue but not plasma IGF-1 levels, as determined by enzyme-linked immunosorbent assay, significantly increased after plantar incision. Immunohistochemistry revealed that IGF1R was predominantly expressed in neurons as well as in satellite glial cells in the dorsal root ganglion (DRG). Double-labeling immunohistochemistry showed that IGF1R expression colocalized with peripherin and TRPV1, but not with NF200 in DRG neurons. The IGF1R inhibitor successfully alleviated mechanical allodynia, heat hyperalgesia, and spontaneous pain behavior observed after plantar incision. Expression of phosphorylated Akt in DRG neurons significantly increased after plantar incision and was suppressed by IGF1R inhibition. These results demonstrate that increased tissue IGF-1 production sensitizes primary afferent neurons via the IGF1R/Akt pathway to facilitate pain hypersensitivity after tissue damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count / methods
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay / methods
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Hyperalgesia / drug therapy
  • Hyperalgesia / etiology*
  • Hyperalgesia / metabolism*
  • Insulin-Like Growth Factor I / adverse effects*
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Oncogene Protein v-akt / metabolism
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Podophyllotoxin / analogs & derivatives
  • Podophyllotoxin / therapeutic use
  • Postoperative Complications / pathology
  • Postoperative Complications / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Receptor, IGF Type 1 / metabolism
  • Receptor, IGF Type 1 / pharmacology
  • Skin / metabolism


  • picropodophyllin
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Oncogene Protein v-akt
  • Podophyllotoxin