Table 4.

Summary of the alterations of apoptotic activities in the spinal dorsal horn in different models of rats and mice.

Reference	Animal Models	Apoptotic Activities	IHC Findings	Effects of Therapeutic Agents (Inhibit Apoptosis)
Schaeffer et al., 2010 [17]	Rats with chronic constriction injury (CCI).	TUNEL assay activities in the spinal cord did not increase on days 5, 15, and 30 after nerve injury.	Nil.	Nil.
Campana et al., 2003 [14]	Rats with spinal nerve crush (SNC) injury.	TUNEL assay activities in the spinal cord did not increase on day 2 after nerve injury.	Nil.	Subcutaneous administration of recombinant human erythropoietin (rhEpo) 1 day before nerve injury reduced pain behavior from day 2 to day 14 after nerve injury.
Siniscalco et al., 2007 [19]	Mice with chronic constriction injury (CCI).	Bax, apoptotic protease-activating factor-1 (apaf-1), caspase-9 mRNA expressions, and TUNEL and caspase-3 activities increased on day 3 after nerve injury.	TUNEL activities were co-stained with NeuN on day 3 after nerve injury.	Intraperitoneal phenyl-N-tert-butylnitrone (ROS scavenger) suppressed pain behavior from day 1 to day 3 after nerve injury and decreased apoptotic activities in the spinal cord on day 3 after nerve injury.
Hu et al., 2015 [20]	Rats with chronic constriction injury (CCI).	TNF-α and caspase-3 mRNA expressions and TUINEL activities increased on day 3 and day 7 after nerve injury, respectively.	Nil.	HBO suppressed pain behavior and apoptotic activities in the spinal cord of rats with CCI on day 3 and day 7 after nerve injury.
Fu et al., 2017 [21]	Rats with chronic constriction injury (CCI).	The number of cleaved caspase-3 and cytochrome C positive neurons increased on day 8 and day 14 after nerve injury.	Cytochrome C was co-stained with NeuN (neuron marker).	Daily HBO therapy suppressed pain behavior and apoptotic activities in the spinal dorsal horn of rats with CCI.
Polga’r et al., 2005 [66]	Mice with spared nerve injury (SNI).	TUNEL assay and cleaved caspase-3 activities did not demonstrate in the apoptotic neurons in the dorsal spinal cord 1 week after nerve injury.	TUNEL activities were co-stained with Iba1 (microglia marker).	Nil.
Chen et al., 2020 [22]	Mice with neuropathic pain induced by vincristine.	Cleaved caspase 3, Bax, and cytochrome c (Cyt-c) increased on day 9 after five consecutive vincristine administrations.	Nil.	Mitoquinone (antioxidant) treatment after vincristine injury suppressed pain behavior of mice, ROS production, and apoptotic activities in the spinal cord of mice.