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Updated: Aug 26, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Substance P microinjected into the periaqueductal gray matter induces antinociception and is released following
Annika Rosén1, Yu-Xuan Zhang, Irene Lund
1Department of Odontology, Division of Oral and Maxillofacial Surgery, Karolinska Institutet, Huddinge Hospital, Box 4064, SE-141 04 Huddinge, Sweden. annika.rosen@ofa.ki.se
Abstract:
The aims of the present study were to investigate, in rats, the behavioral effects of substance P (SP) microinjected into the ventrolateral periaqueductal gray (PAG) and the effects of the neurokinin 1 (NK-1) receptor antagonist [d-Arg1, d-Trp7, 9, Leu11]-substance P (Spantide). The effect of morphine administration on the release of SP in the ventrolateral PAG was also investigated using microdialysis in awake rats. SP microinjected into the ventrolateral part of the PAG induced significant increases in the hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation as an antinociceptive response. The NK-1 receptor antagonist blocked these effects but exhibited no antinociceptive effect alone. Subcutaneous administration of morphine increased basal SP-like immunoreactivity (SP-LI) release in the microdialysate obtained from the ventrolateral PAG of freely moving rats. Our results demonstrate that SP injected into the ventrolateral PAG induces an antinociceptive effect via activation of NK-1 receptors. Morphine administered systemically induces the release of SP in the ventrolateral PAG. We suggest that an increased release of SP in the PAG may contribute to opioid antinociception.
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