Table A1.

Most frequently encountered conditions or diseases causing neuropathic pain in the emergency department. Each of these conditions and disorders listed in the table may present in the emergency department with acute or chronic pain.

Peripheral Neuropathic Pain Syndromes	Physiopathological Mechanisms
1.  Postherpetic neuralgia	Reactivation of the virus leads to inflammatory immune responses that destroy both peripheral and central neurons and stimulate an abnormal reorganization of the pain stimulus transmission system. Reduced threshold of action potentials due to peripheral and central sensitization up-regulates the receptors linked with pain (e.g., TRPV1), increases the proportion of VGCSa and VGKCs, and causes loss of GABAergic inhibitory interneurons at the DHs.
2.  Painful polyneuropathy	Diabetic polyneuropathy: Abnormal activity of nociceptive fibers due to oxidative and nitrosative stress (e.g., polyol pathway hyperactivity), microvascular impairment (nerve hypoxia altering electrical stability), and activation of microglia. Increased peripheral input induces hyperactivity of DHs (augmentation of NMDAR expression) and neuroplastic changes in central sensory neurons. GBS: Inflamed or damaged large myelinated sensory fibers causing dysesthesia and muscle pain in the extremities, stimulation of the spinal roots by high concentrations of CSFP levels, and small-fiber sensory impairments Chemotherapy-induced peripheral neuropathy: Mitochondrial dysfunction, changes in calcium homeostasis, oxidative stress, activation of apoptotic pathways, loss of myelinated and unmyelinated fibers, activation of the immune system, and increased ion channel expression
3.  Traumatic injury of peripheral nerves	Ectopic impulses generated at the site of nerve injury or the DRG, low-grade inflammation, and pro-inflammatory cytokines
4.  Back and neck pain and cervical and lumbosacral radiculopathies	Mechanical compression, vascular congestion, and peri- and intraradicular fibrosis of the DRG. Ectopic pulse generation is generated by inflammation around the nerve root (e.g., substances and breakdown products released from the nucleus pulposus in degenerating disks, inducing inflammatory responses).
Central Neuropathic Pain Syndromes	Physiopathological Mechanisms
1.  Central post-stroke pain	Disinhibition theory: Loss of STT input to the posterior lateral part of the thalamus causes disinhibition of the medial thalamus, leading to pain (preferential involvement of the nondominant thalamus). Dynamic reverberation theory: Pain arises due to improper oscillatory patterns in the loop running between the thalamus and cortex. Disinhibition of the medially located spino-reticulothalamic or paleospinothalamic pathways by a lesion of the lateral spinothalamic tract Changes in descending inhibition and facilitation from the rostral ventromedial medulla and the mesencephalic reticular formation
2.  Multiple sclerosis-related neuropathic pain conditions	Demyelinating plaque on the dorsal column of the cervical spinal cord (Lhermitte’s sign) Demyelination of primary afferents at the trigeminal nerve root entry zone (trigeminal neuralgia secondary to MS) Pro-inflammatory cytokines induce permeability changes in the blood–brain barrier to facilitate leukocyte infiltration and neuroinflammation.
3.  Spinal cord injury-related central neuropathic pain	At-level neuropathic pain: Nerve root lesion or compression causes deafferentation and ectopic impulse generation, inducing and maintaining hyperexcitability of central wide dynamic neurons. Below-level neuropathic pain: The spinothalamic tract projection neurons below the spinal injury may be lesioned and give rise to deafferentation hyperexcitability in higher-order neurons, including the thalamus.
Cranial Neuropathies	Physiopathological Mechanisms
1.  Trigeminal neuralgia	Neurovascular compression: Proximal compression of the trigeminal sensory root near the brainstem (root entry zone) by a blood vessel (artery or vein) Abnormal functioning of ion channels results in neuronal hyperexcitability.
2.  Glossopharyngeal neuralgia	Neurovascular compression: Compression of the glossopharyngeal nerve by the posterior inferior cerebellar artery (PICA) Entrapment of the nerve by an elongated styloid process (Eagle syndrome), cerebellopontine angle, and cranial base tumors
3.  Nervus intermedius neuralgia	Facial nerve inflammation disorders (e.g., Ramsay–Hunt syndrome, Bell’s palsy)
4.  Occipital neuralgia	Neurovascular compression: compression of the occipital nerve by close proximity of the occipital artery in the peripheral course Entrapment of the nerves by the atlanto-epistrophic ligament and compression due to a trigger point or myofascial spasm Tumors (e.g., osteochondroma of the cervical vertebra to neuromas) and Arnold–Chiari malformations Posterior head trauma, including fractures and whiplash injuries

HZ: Herpes Zoster; TRPV1: transient receptor potential vanilloid; VGCSs: voltage-gated sodium channels; VGKCs: potassium voltage-gated channels; DHs: dorsal horns; NMDA: spinal N-Methyl-D-aspartate; CSFP: cerebrospinal fluid protein; STT: spinothalamic tract; MS: multiple sclerosis; DRG: dorsal root ganglion.