A 28-year-old woman comes to the office due to pain at a previous surgery site. The patient underwent cesarean delivery a year ago and had no issues with wound healing. However, over the past 2 months, she has had intermittent sharp and burning pain at the incision site. Physical examination reveals a well-healed, low, transverse scar. There is a small knot palpable at the left end of the scar, light touch of which elicits severe pain. Cutaneous sensory nerve injury and abnormal axonal regeneration are suspected. Which of the following ion channels is most likely upregulated within the affected axons?

Question

A 28-year-old woman comes to the office due to pain at a previous surgery site.  The patient underwent cesarean delivery a year ago and had no issues with wound healing.  However, over the past 2 months, she has had intermittent sharp and burning pain at the incision site.  Physical examination reveals a well-healed, low, transverse scar.  There is a small knot palpable at the left end of the scar, light touch of which elicits severe pain.  Cutaneous sensory nerve injury and abnormal axonal regeneration are suspected.  Which of the following ion channels is most likely upregulated within the affected axons?

Quizplus · Accepted Answer

This patient likely suffered cutaneous nerve damage during her surgical procedure. Transected nerves undergo wallerian degeneration, which involves axonal dissolution while activated Schwann cells and macrophages degrade myelin. In addition to clearing cellular debris, Schwann cells and macrophages stimulate formation of a growth cone from the proximal axon stump to facilitate nerve regeneration. However, if the regenerating axons cannot find their distal target, regeneration can result in formation of a disorganized mass of axonal processes, Schwann cells, vascular hyalinization, and fibrosis known as a neuroma. Chronic axonal injury or inflammation (such as occurs with a neuroma) induces increased expression of voltage-gated sodium channels, which are important for the generation and propagation of action potentials. The density of voltage-gated sodium channels correlates with the excitability of nerves; therefore, the upregulated sodium channels in injured nerves and neuromas increase nociceptive (pain) sensitivity. To support the diagnosis of a neuroma, local anesthetic, which blocks sodium channels in the neuronal cell membrane, is administered to prevent depolarization of the nerve. This often provides immediate relief of pain. (Choice A) Action potential propagation depends on voltage-gated calcium channels in certain cardiac conduction tissues (eg, sinoatrial and atrioventricular nodes). However, peripheral nerve depolarization is driven primarily by sodium, rather than calcium, influx. (Choice B) The influx of negative chloride ions often causes hyperpolarization, which inhibits formation of action potentials. (Choice C) Magnesium selective ion channels are not directly involved in nerve depolarization. However, magnesium ions block calcium channels, preventing calcium influx at the axon terminal. This impairs release of neurotransmitter vesicles into the synapse, inhibiting impulse transmission. (Choice D) The efflux of potassium out of the cell leads to hyperpolarization. Therefore, upregulation of potassium channels would tend to keep the membrane potential away from the depolarization threshold, leading to less signal transmission (ie, less pain). Educational objective: A neuroma forms when regenerating axons are unable to find their distal target and create a haphazard mass of axons and supporting cells. Upregulation of voltage-gated sodium channels, which generate and propagate action potentials, is likely responsible for the increased pain of these lesions.

A 28-Year-Old Woman Comes to the Office Due to Pain