Neuropathic Pain Medical Definition

Neuropathic pain involves injury or alteration of the normal sensory and modulatory nervous systems.⁴⁸Dunteman ED. Mechanisms and treatment issues for neuropathic pain. CAN J ANESTH. 2004. pR2.

Painful neuropathies can result from a broad range of etiologies, including metabolic and endocrinologic disorders such as diabetes and liver disease, infection, demyelinating disorders, stroke and spinal cord injuries, malignancies, and other causes.⁴⁸Dunteman ED. Mechanisms and treatment issues for neuropathic pain. CAN J ANESTH. 2004. pR2.

These changes can produce a set of neuropathic symptoms that are often difficult to treat. Multiple changes may occur in the injured neural structures. ⁴⁹Dunteman ED, CAN J ANESTH 2004 / 51: 6 / pR1.

Assessing & diagnosing neuropathic pain

Changes may also occur in areas not directly injured—often distant from the original insult. The resulting pain complaints include spontaneous “burning” sensations, with intermittent sharp, lightening-like stabbing and shooting pain. Marked sensitivity and pain may be elicited by minimal stimulation such as a light touch, a slight breeze, or a temperature change.⁵⁰Dunteman ED, CAN J ANESTH 2004 / 51: 6 / pR1.

Neuropathic pain involves injury or alteration of the normal sensory and modulatory nervous systems and can include abnormal nerve regenerations, increased expression of membrane sodium channels, diminution of inhibitory mechanisms, and decreased expression of mu-opioid receptors. ⁵¹Ahlawat A. Comprehensive review on molecular mechanisms of neuropathic pain. Journal of Innovations in Pharmaceutical and Biological Sciences. 2017. p1^,52 Meacham K et al. Neuropathic Pain: Central vs. Peripheral Mechanisms. Curr Pain Headache Rep. 2017. p28 ^,53Zhou XL et al. Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain. Molecular Pain 2014. p1-2

Abnormal nerve regeneration

Abnormal nerve regeneration may occur following peripheral nerve damage, leading to the formation of a neuroma at the nerve trunk. These nerve sprouts can generate spontaneous discharge leading to a sensation of pain.⁵⁴Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014 Feb 5; 348:f7656, p4^,55 Meacham K et al. Neuropathic Pain: Central vs. Peripheral Mechanisms. Curr Pain Headache Rep. 2017. p28.

Increased expression of membrane sodium channels

Increased expression of sodium channel subtypes with lowered activation thresholds on axons of damaged nerves is believed to underlie ectopic impulse generation after peripheral nerve injury.⁵⁶Meacham K et al. Neuropathic Pain: Central vs. Peripheral Mechanisms. Curr Pain Headache Rep. 2017. p27-28

The altered expression of sodium channels lowers the threshold of activation, facilitating repetitive firing of the injured neurons and generating the sensation of pain.⁵⁷Truini A et al. Reappraising neuropathic pain in humans-how symptoms help disclose mechanisms. Nat. Rev. Neurol. 9, 572-582. 2013. p575.

Disinhibition

Loss of inhibitory mechanisms following peripheral nerve injury can also lead to hypersensitivity and spontaneous pain. A substantial loss of GABA-mediated inhibition occurs after peripheral nerve injury due to selective death of GABA-ergic neurons in the dorsal horn of the spinal cord leading to an inability for normal inhibition of pain signals, potentially lowering the perceived threshold of pain.⁵⁸ Alves JM, Lin K. Neuropathic Pain: A Review of Interneuronal Disinhibition. Arch Neurosci. 2018. P1,3^,59Moore KA et al. Partial Peripheral Nerve Injury Promotes a Selective Loss of GABAergic Inhibition. Journal of Neuroscience. 2002. p6730.

Decreased expression of mu-opioid receptors

Decreased expression of mu-opioid receptors in dorsal root ganglion neurons and spinal neurons can contribute to disinhibition after peripheral nerve injury. This down-regulation of opioid receptors corroborates with the attenuation of the effects of opioids or other analgesics in neuropathic pain management.⁶⁰Zhou XL et al. Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain. Molecular Pain 2014. p1-2.