Cold hypersensitivity increases with age in mice with sickle cell disease

Area of Science:

• Neuroscience
• Pain Research
• Genetics

Background:

• Sickle cell disease (SCD) is characterized by vaso-occlusive crises and chronic pain.
• Individuals with SCD exhibit heightened cold sensitivity, but the underlying mechanisms and age-related progression are poorly understood.

Purpose of the Study:

• To investigate the mechanisms of cold hypersensitivity in a mouse model of SCD.
• To determine if cold sensitivity progresses with age in SCD mice.

Main Methods:

• Thermotaxis behavior was assessed in young and aged sickle cell disease (SCD) mice using a cold preference test.
• Peripheral C-fiber activity was recorded in skin-nerve preparations to evaluate cold detection thresholds.
• mRNA expression levels of cold-sensing ion channels (TRPM8, TRPA1, TREK-1, TREK-2, TRAAK) and other pain-related genes were quantified.

Main Results:

• SCD mice exhibited significantly increased cold sensitivity compared to controls.
• Cold hypersensitivity worsened with advanced age in SCD mice.
• C-fibers from SCD mice showed lower cold detection thresholds.
• While expression of key cold-sensing ion channels remained unchanged, mRNA levels for endothelin 1 and tachykinin receptor 1 were elevated in SCD mice.

Conclusions:

• Age-dependent cold hypersensitivity is a prominent feature in sickle cell disease mouse models.
• The findings suggest that altered expression of specific pain-related genes, such as endothelin 1 and tachykinin receptor 1, may contribute to cold hypersensitivity in SCD, rather than changes in major cold-sensing ion channels.