Endomorphins suppress nociception-induced c-Fos and Zif/268 expression in the rat spinal dorsal horn

Tateyama, Shingo; Ikeda, Tetsuya; Kosai, Kazuko; Nakamura, Tadashi; Kasaba, Toshiharu; Takasaki, Mayumi; Nishimori, Toshikazu

doi:10.1016/s0014-2999(02)02196-9

Cited by 6 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B. et al, 2015) along the spinal nociceptive transmission pathway. Spinal administration of EM2 has been demonstrated to alleviate nociceptive behaviors in inflammatory pain (Tateyama et al, 2002; Zhao et al, 2015), cancer pain (Chen L. et al, 2015) and peripheral neuropathic pain models (Przewlocka et al, 1999). However, there are few reports concerning the analgesic effects of EM2 at the spinal level in the DNP model.…”

Section: Introductionmentioning

confidence: 99%

Endomorphin-2 Inhibition of Substance P Signaling within Lamina I of the Spinal Cord Is Impaired in Diabetic Neuropathic Pain Rats

Wan

Bai

Kou

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Opiate analgesia in the spinal cord is impaired in diabetic neuropathic pain (DNP), but until now the reason is unknown. We hypothesized that it resulted from a decreased inhibition of substance P (SP) signaling within the dorsal horn of the spinal cord. To investigate this possibility, we evaluated the effects of endomorphin-2 (EM2), an endogenous ligand of the μ-opioid receptor (MOR), on SP release within lamina I of the spinal dorsal horn (SDH) in rats with DNP. We established the DNP rat model and compared the analgesic efficacy of EM2 between inflammation pain and DNP rat models. Behavioral results suggested that the analgesic efficacy of EM2 was compromised in the condition of painful diabetic neuropathy. Then, we measured presynaptic SP release induced by different stimulating modalities via neurokinin-1 receptor (NK1R) internalization. Although there was no significant change in basal and evoked SP release between control and DNP rats, EM2 failed to inhibit SP release by noxious mechanical and thermal stimuli in DNP but not in control and inflammation pain model. We also observed that EM2 decreased the number of FOS-positive neurons within lamina I of the SDH but did not change the amount of FOS/NK1R double-labeled neurons. Finally, we identified a remarkable decrease in MORs within the primary afferent fibers and dorsal root ganglion (DRG) neurons by Western blot (WB) and immunohistochemistry (IHC). Taken together, these data suggest that reduced presynaptic MOR expression might account for the loss of the inhibitory effect of EM2 on SP signaling, which might be one of the neurobiological foundations for decreased opioid efficacy in the treatment of DNP.

show abstract