Histochemical analysis of the biphasic properties of formalin pain-induced behavior

Ikuei Hirota1, Yoshihisa Koyama1,2, Shoichi Shimada1,2

  • 1Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.

Insights

Formalin-induced pain in mice shows distinct spinal cord activity patterns. Deep spinal cord neurons are active in the first phase, while superficial neurons activate in the second, offering new pain treatment targets.

Area of Science:

  • Neuroscience
  • Pain Research
  • Histochemistry

Background:

  • The formalin test is a standard method for assessing pain in mouse models.
  • While formalin-induced pain behavior is well-documented, detailed histochemical analysis of central nervous system activity, particularly concerning biphasic pain properties, is limited.

Purpose of the Study:

  • To investigate the changes in spinal neuronal activity during formalin-induced pain.
  • To elucidate the specific spinal cord regions involved in the distinct phases of formalin-induced pain.

Main Methods:

  • Utilized immunofluorescent staining with c-Fos antibodies to mark neuronal activity in mice.
  • Administered 2% formalin to induce acute pain and analyzed spinal dorsal horn activity.
  • Conducted comparative studies using lower concentrations of formalin (0.25%) and capsaicin.

Main Results:

  • Observed phase-specific neuronal activity in the spinal dorsal horn.
  • High neural activity in deep regions (layers V-VII) during the first phase of formalin pain.
  • Increased neural activity in superficial regions (layers I-III) during the second phase of formalin pain.
  • Low concentrations of formalin and capsaicin, lacking distinct biphasic properties, showed activity only in superficial spinal dorsal horn regions.

Conclusions:

  • The biphasic nature of formalin-induced pain is linked to the differential activation of deep and superficial spinal cord neurons.
  • Targeting deep spinal cord neurons may offer novel therapeutic strategies for allodynia and chronic pain conditions.