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Unexpected Role of TNFα Signaling in the Resolution of Postoperative Pain in Mice

Sophie Laumet1, Aaryn M Edwards1, Kufreobong E Inyang1

  • 1Department of Physiology, Michigan State University, East Lansing, MI, USA.

Journal of Pain Research
|November 19, 2025
PubMed

Insights

Tumor necrosis factor (TNFα) signaling is crucial for resolving acute pain. Blocking TNFα paradoxically prolongs pain hypersensitivity, highlighting its essential role in preventing chronic pain development.

Area of Science:

  • Immunology
  • Neuroscience
  • Pain research

Background:

  • The transition from acute to chronic pain is not well understood.
  • Immune cells and inflammation may play a role in pain resolution.

Purpose of the Study:

  • To investigate the role of tumor necrosis factor alpha (TNFα) signaling in the resolution of acute postoperative pain.
  • To determine if inhibiting TNFα signaling affects pain duration and prevents chronic pain.

Main Methods:

  • A mouse model of postoperative pain (plantar incision) was used.
  • Mice were treated with anti-TNFα antibodies or Etanercept to block TNFα signaling.
  • Pain hypersensitivity was measured in male and female mice.

Main Results:

  • Inhibition of TNFα signaling significantly delayed the resolution of pain hypersensitivity.
  • Early blockade of TNFα did not reduce pain but extended its duration.
  • These effects were observed in both male and female mice.

Conclusions:

  • TNFα signaling plays a critical, albeit paradoxical, role in resolving acute pain.
  • Blocking TNFα early in the pain process can prolong pain and potentially contribute to chronicity.
  • Immune signaling is essential for initiating pain resolution and preventing pain persistence.
Keywords:
TNFαinflammationmicepain resolutionpostoperative pain

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