This patient with long-standing diabetes mellitus has tingling/burning pain in the feet, loss of vibration sensation, and loss of ankle reflexes, indicating distal symmetric polyneuropathy (diabetic neuropathy).  Long-standing diabetes mellitus is often associated with damage to the distal axons of sensory neurons due to the accumulation of cross-linked glycosylated serum proteins in the vaso nervorum, which causes inflammation, vasoconstriction, and neuronal oxidative stress.  Initial symptoms include tingling, numbness, and burning pain in the toes and/or feet.  Sensation to pain, light touch, temperature, vibration, and proprioception are generally diminished in the affected area.  Babinski and ankle reflex are often absent.

Treatment includes glycemic control and foot care to limit the development of ulcers and need for amputation.  Patients with painful neuropathy also typically receive a serotonin-norepinephrine reuptake inhibitor (eg, duloxetine, venlafaxine), a gabapentinoid (eg, pregabalin, gabapentin), or a tricyclic antidepressant such as amitriptyline.  Amitriptyline modulates pain transmission by inhibiting voltage-gated sodium channels in sensory nerves, blocking NMDA (excitatory) receptors in the spinal cord, and altering norepinephrine signaling in the brain.

(Choice B)  Benzodiazepines (eg, clonazepam) are often used for anxiety, muscle relaxation, or nausea.  They are not typically used for neuropathic pain.

(Choice C)  Although selective serotonin reuptake inhibitors (eg, fluoxetine) are often used for depression and anxiety, they are not often employed for neuropathic pain.  In contrast, serotonin-norepinephrine reuptake inhibitors (eg, duloxetine, venlafaxine) are often used as first-line treatment to manage painful diabetic neuropathy; these agents alter central transmission of pain by increasing norepinephrine in the central synapses.

(Choice D)  Nonsteroidal anti-inflammatory drugs such as naproxen are prescribed for acute painful conditions such as back pain, muscle strain, or bone fracture.  However, they have limited efficacy for neuropathic pain.

(Choice E)  Opioid pain medications (eg, oxycodone) are not recommended for most patients with neuropathic pain due to their questionable efficacy and risk of dependence.  Patients with neuropathic pain should first be given a trial of an antidepressant or gabapentinoid.

(Choice F)  Certain patients taking isoniazid require pyridoxine supplementation to prevent the development of drug-induced peripheral neuropathy.  This patient is not taking isoniazid; therefore, pyridoxine supplementation would not be helpful.

Educational objective:
Patients with long-standing, poorly controlled diabetes mellitus are at high risk for developing distal symmetric polyneuropathy (diabetic neuropathy).  Symptoms generally include progressive numbness, tingling, and burning/stabbing pain in the feet and/or toes that progresses proximally.  Painful neuropathy is treated with serotonin-norepinephrine reuptake inhibitors, gabapentinoids, or tricyclic antidepressants.