Journal of Signal Transduction not activate ERK1/2 in the Arc and the PVN [60]. These activations might be involved in autonomic and endocrine responses to the stress. Those functions remain elusive, however. 3. Conclusions and Perspectives The noxious stimuli induced activations of MAPKs in the components of descending pain modulatory sys- tem. The activations in these components were asso- ciated with pain perception and pain-related emotional responses (Figure 2). In addition, psychophysical stress also activated MAPKs in these structures. They seem to be mainly related to depressive-like behavior (Figure 3). MAPKs are involved in both transcription-independent and transcription-dependent forms of central sensitization. Stress-induced neural plasticity in these structures via acti- vations of MAPKs might aﬀect nociceptive processing. In turn, the noxious stimuli-induced neural plasticity might potentiate depressive-like behavior in response to psycholog- ical stress. Clinical studies have demonstrated a reciprocal interaction between emotionality and pain perception in chronic pain conditions [93]. Elucidation of their physiolog- ical functions might contribute to a better understanding of chronic pain and lead to the development of new treatment to a variety of pain syndromes. Recently, several studies have demonstrated that activa- tion of ERK5 in the dorsal root ganglion and the spinal dorsal horn is related to hyperalgesia and allodynia following peripheral tissue injury [94–96]. Although there is no study that has examined the noxious stimuli-induced ERK5 acti- vation in the supraspinal structures such as descending pain modulation system, one study has reported a reduction of ERK5 activity in the frontal cortex following psychophysical stress [97]. More importantly, PD98059 and U0126, speciﬁc inhibitors of MEK1/2-ERK1/2, also inhibit MEK5-ERK5 pathway [98]. 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