EGFR has also been demonstrated to mediate opioid tolerance in several rodent models, including two chronic pain models of spinal nerve ligation (SNL)-induced peripheral neuropathies and cancer-induced bone pain (CIBP) [25,94] and pre-tolerance in morphine-naive rats [25] (summarized in Table 2) where enhanced EGFR signaling can aggravate while suppression of EGFR signaling can alleviate morphine tolerance [25,94]. Here, EGFR is linked to cancer.