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Updated: Mar 29, 2026
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Altered nociception and morphine tolerance in neuropeptide FF receptor type 2 over-expressing mice
1Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan.
Background:
The neuropeptide FF system is thought to act as an anti-opioid modulator and plays a role in nociception, morphine antinociception and dependence. Two receptor subtypes, NPFFR1 and NPFFR2, have been identified, but their respective roles in these processes remain uncertain.
Methods:
In the present study, the role of NPFFR2 was investigated using transgenic mice over-expressing NPFFR2 in addition to a NPFFR2 agonist AC-263093.
Results:
NPFFR2 Tg mice exhibited increased sensitivity to both mechanical and thermal noxious stimuli compared to the WT mice, while the antinociceptive effects of morphine at three different doses (6.25, 12.5 and 25 mg/kg, s.c.) were similar in both strains. The development of tolerance to morphine antinociception after chronic morphine treatment (12.5 mg/kg, s.c.; twice daily × 5 days) was attenuated in NPFFR2 Tg mice when compared to WT mice. Similarly, WT mice receiving AC-263093 pretreatment (2.5 mg/kg, i.p.) showed attenuated morphine tolerance compared to vehicle controls. Most naloxone-precipitated morphine withdrawal symptoms were not attenuated in NPFFR2 Tg mice, with the exception of wet dog shake that was significantly reduced. Both NPFFR2 Tg and WT mice displayed similar degree of morphine rewarding.
Conclusions:
Our results suggest that neuropeptide FF R2 is mainly involved in the modulation of nociception and tolerance to morphine antinociception.
Insights
The neuropeptide FF receptor 2 (NPFFR2) system modulates pain perception and reduces tolerance to morphine's pain-relieving effects. Overexpressing NPFFR2 in mice increased pain sensitivity but attenuated morphine tolerance.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The neuropeptide FF system acts as an anti-opioid modulator, influencing nociception, morphine antinociception, and dependence.
- Two receptor subtypes, NPFFR1 and NPFFR2, have been identified, but their specific roles are unclear.
Purpose of the Study:
- To investigate the role of neuropeptide FF receptor 2 (NPFFR2) in nociception and morphine antinociception and dependence.
Main Methods:
- Utilized transgenic mice overexpressing NPFFR2 (NPFFR2 Tg) and a NPFFR2 agonist (AC-263093).
- Assessed nociceptive sensitivity (mechanical and thermal) and morphine antinociception in NPFFR2 Tg and wild-type (WT) mice.
- Evaluated the development of morphine tolerance and precipitated withdrawal symptoms.
Main Results:
- NPFFR2 Tg mice showed increased sensitivity to noxious stimuli but similar morphine antinociceptive effects compared to WT mice.
- Morphine tolerance development was attenuated in NPFFR2 Tg mice and in WT mice pretreated with the NPFFR2 agonist.
- Most morphine withdrawal symptoms were unaffected, except for a reduction in wet dog shakes in NPFFR2 Tg mice.
Conclusions:
- Neuropeptide FF receptor 2 (NPFFR2) plays a significant role in modulating nociception.
- NPFFR2 is involved in regulating the development of tolerance to morphine antinociception.
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