Peripheral Leptin Signaling Mediates Formalin-Induced Nociception

Neurosci Bull. 2018 Apr;34(2):321-329. doi: 10.1007/s12264-017-0194-2. Epub 2017 Dec 5.


Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.

Keywords: Formalin test; Leptin; Nociception; Obesity.

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Leptin / metabolism*
  • Leptin / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nociception / drug effects
  • Nociception / physiology*
  • Nociceptive Pain / etiology
  • Nociceptive Pain / metabolism*
  • Obesity / complications
  • Obesity / metabolism*
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Receptors, Leptin / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Leptin
  • Receptors, Leptin
  • leptin receptor, mouse