High-fat diet causes mechanical allodynia in the absence of injury or diabetic pathology.
Jessica A TierneyCalvin D UongMelissa E LenertMarisa WilliamsMichael D D BurtonPublished in: Scientific reports (2022)
Understanding the interactions between diet, obesity, and diabetes is important to tease out mechanisms in painful pathology. Western diet is rich in fats, producing high amounts of circulating bioactive metabolites. However, no research has assessed how a high-fat diet (HFD) alone may sensitize an individual to non-painful stimuli in the absence of obesity or diabetic pathology. To investigate this, we tested the ability of a HFD to stimulate diet-induced hyperalgesic priming, or diet sensitization in male and female mice. Our results revealed that 8 weeks of HFD did not alter baseline pain sensitivity, but both male and female HFD-fed animals exhibited robust mechanical allodynia when exposed to a subthreshold dose of intraplantar Prostaglandin E 2 (PGE 2 ) compared to mice on chow diet. Furthermore, calcium imaging in isolated primary sensory neurons of both sexes revealed HFD induced an increased percentage of capsaicin-responsive neurons compared to their chow counterparts. Immunohistochemistry (IHC) showed a HFD-induced upregulation of ATF3, a neuronal marker of injury, in lumbar dorsal root ganglia (DRG). This suggests that a HFD induces allodynia in the absence of a pre-existing condition or injury via dietary components. With this new understanding of how a HFD can contribute to the onset of pain, we can understand the dissociation behind the comorbidities associated with obesity and diabetes to develop pharmacological interventions to treat them more efficiently.
Keyphrases
- high fat diet
- insulin resistance
- high fat diet induced
- type diabetes
- weight loss
- neuropathic pain
- adipose tissue
- physical activity
- metabolic syndrome
- spinal cord
- skeletal muscle
- glycemic control
- chronic pain
- high glucose
- weight gain
- spinal cord injury
- body mass index
- diabetic rats
- pain management
- single cell
- wound healing
- cell proliferation
- south africa
- blood brain barrier
- drug induced
- brain injury
- poor prognosis
- drug delivery
- stress induced
- long non coding rna