CNS: Diabetic peripheral neuropathy (Exam 2 Material)

What is diabetic peripheral neuropathy, and what are its symptoms and complications?

• Diabetic peripheral neuropathy: Damage to peripheral nerves (PNS) caused by diabetes, particularly from chronically elevated blood glucose

• Epidemiology: Affects approx 1/3 to ½ of people with diabetes

• Location: Feet/legs; sometimes hands/arms

• Symptoms: Numbness, weakness, burning, tingling; pain worse at night

• Complications: Sores, blisters, falls, mental health effects, charcot foot, and possible amputation

How does diabetic peripheral neuropathy cause the previously talked abt complications?

• Diabetes results in chronic high blood glucose → peripheral nerve damage

• This nerve damage leads to:

  • Loss of sensation: Injuries go unnoticed → blisters, sores, infections

  • Abnormal/excessive signaling: Damaged sensory nerves send inappropriate pain signals

    • Leads to burning, tingling, shooting pain

  • Loss of motor signaling: Poor balance → falls, fractures, muscle weakness

• This can lead to: Severe complications → foot deformity or possible amputation

What is Charcot foot?

• A complication of severe diabetic peripheral neuropathy in which bones and joints become damaged and deformed

• B/c the patient has reduced sensation, repeated injuries or fractures may go unnoticed

• This can cause the arch of the foot to collapse, producing a rocker-bottom deformity

With diabetic neuropathy:

1. High glucose damages peripheral sensory nerves.

2. These nerves cannot properly communicate the position of your feet to your brain OR can’t communicate that there is pain.

3. Your brain has difficulty determining where your feet are.

4. Balance becomes impaired → increased risk of falls.

What are the 6 risk factors of diabetic peripheral neuropathy?

• Smoking

• Heavy drinking

• Hypertension

• Obesity

• High cholesterol

• Kidney disease

What are the three main mechanisms of diabetic peripheral neuropathy?

1. Microvascular changes (nerve damage)

• Chronically high blood glucose damages the small blood vessels supplying peripheral nerves

• This reduces the delivery of oxygen and essential nutrients to neurons

• Neurons become damaged and cannot function properly

• Result: Loss of normal nerve function → numbness, weakness, and impaired sensation

2. Hyperexcitability of sensory neurons (increased pain)

• Normally, nociceptors generate action potentials in response to harmful stimuli

• In diabetic neuropathy, changes in ion channels make these neurons easier to activate

• ↑ Na⁺ channels or ↓ Shaker K⁺ channels (reduces the ability to oppose depolarization) → increased firing and ectopic neuronal activity → pain

  • Ectopic neuronal activity: Action potentials occur in abnormal locations along the nerve, sometimes without an appropriate harmful stimulus.

3. Inflammation (amplifies pain)

• Diabetes-associated nerve injury promotes activation of microglia in the spinal cord

• Activated microglia release pro-inflammatory mediators

• These mediators increase neuronal excitability in the dorsal horn

• Pain signals become amplified as they travel toward the brain

• Result: Increased pain sensitivity

What are the treatments of diabetic peripheral neuropathy? [skipped come back]

• Main Idea: These medications treat the pain caused by nerve damage, not the underlying nerve damage itself

• Lidocaine (topical anesthetic): Blocks voltage-gate sodium channels so that the signal cannot be transmitted

• Tricyclic antidepressants: Block reuptake of NE in the spinal cord

  • Normally, when NE is taken back, there’s less NE to suppress the pain

  • Blocking NE reuptake → more NE remains available → stronger inhibition of pain signaling

  • Result: ↓ Pain transmission in the spinal cord → ↓ pain

• Gabapentin: Inhibits presynaptic voltage-gated Ca²⁺ channels by disrupting the regulatory function of a channel subunit

  • Normally, Ca²⁺ enters the presynaptic terminal → triggers release of neurotransmitters such as glutamate.

  • Gabapentin reduces excitatory neurotransmitter release, decreasing pain signaling

  • Result: ↓ E