A 44-year-old man comes to the office due to paresthesia and pain in his feet. The patient began experiencing tingling and numbness in his toes several months ago, which gradually progressed to the rest of both feet. He has also had burning pain on the soles, which frequently disrupts his sleep at night. The patient has a 6-year history of HIV infection. He was not adherent to treatment initially but now takes antiretroviral therapy regularly. His most recent CD4 cell count was 550/mm³. Vital signs are within normal limits. Foot examination shows decreased pain and touch sensation and loss of ankle reflexes bilaterally. There are no other focal neurologic deficits. Medication review shows no neurotoxic drugs and laboratory studies are within normal limits. Treatment with duloxetine is planned. This medication is most likely to improve this patient's symptoms via which of the following mechanisms?

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11ec160b_3c19_124a_9249_c98d59198e14_MD0001_00 This patient with HIV peripheral neuropathy is being treated with duloxetine, a serotonin-norepinephrine reuptake inhibitor (SNRI). Because SNRIs increase norepinephrine in the central synapses, they modulate the descending pain pathway, leading to decreased central perception of pain. First-line therapy for painful neuropathy includes the following 3 classes of medications: (Choice A) Nonsteroidal anti-inflammatory drugs have an analgesic effect that is mediated by decreased sensitization of sensory afferent neurons. They are effective in treating pain due to inflammation but not for neuropathic pain. (Choices B and D) Opioids reduce pain perception at multiple levels. At the spinal level, they lead to decreased substance P-induced activation of dorsal horn neurons. At the supraspinal level, they inhibit GABA release by the periaqueductal gray neurons. They are possibly effective for neuropathic pain, but they are not recommended as initial treatment due to the risk of abuse and dependence. (Choice C) Carbamazepine, an anticonvulsant that works by frequency-dependent blockade of neuronal conductance, is used to treat trigeminal neuralgia. Educational objective: Serotonin-norepinephrine reuptake inhibitors are often used for neuropathic pain. They increase norepinephrine in the central synapses, which modulates the descending pain pathway, leading to decreased central perception of pain.

A 44-Year-Old Man Comes to the Office Due to Paresthesia