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. Author manuscript; available in PMC: 2021 Oct 19.
Published in final edited form as: Handb Behav Neurosci. 2020 Mar 31;26:161–212. doi: 10.1016/B978-0-12-815134-1.00008-8

TABLE 3.

Amygdalar opioid regulation of nociception.

Subregion Manipulation or injection OR Behavioral test or response measured Subjects Summary of findings Overall opiate effect Authors
Amygdala
AMY Morphine, plantar formalin injections MOR fMRI in rats Rats (male) In anesthetized rats, both morphine and intraplantar formalin injections activated the BOLD signal in the amygdala, but pretreatment with morphine attenuated the formalin-induced amygdala activation Morphine activates amygdala Shah et al. (2005)
AMY Morphine, END, naltrexone, naltrindole, βFNA MOR, DOR Tail-flick latencies to heat, jump thresholds with footshock; data pooled from CEA, MEA, and BLA Rats (male) Bilateral injections of morphine and END in amygdala increased latencies in the tail-flick test and jump thresholds to footshock. Effects or amygdala opioids were blocked by injections of naltrexone, naltrindole, and βFNA in the PAG MOR agonist in amygdala is antinociceptive Pavlovic, Cooper, & Bodnar (1996)
AMY Chronic pain models MOR, DOR GTPγS binding, LD Box, EPM Mice Chronic pain (4 weeks) in both sciatic nerve ligation and CFA models induced anxiogenic effects in the LD Box and EPM. GTPγS binding (amygdala homogenates) showed decreased stimulation with DAMGO (MOR) and SNC80 (DOR), but increased stimulation with the KOR agonist ICI 199,441. KOR changes were seen in the CFA model but not the nerve ligation model Chronic pain increases MOR and DOR, but decreases KOR, receptor coupling in amygdala Narita et al. (2006)
Central amygdala
CEA ENK overexpression ENK Formalin-induced nociceptive behaviors Rats (male) Overexpression of ENK in the CEA-reduced phase two flinching behavior in the formalin test that was reversed with naloxone ENK overexpression in CEA is antinociceptive in supra-spinal pain Kang, Wilson, Bender, Glorioso, and Wilson (1998), Kang, Wilson, and Wilson (1999)
CEA Enkephalinase inhibitor SCH-32615, naloxone ENK Licking in hot-plate, tail-flick to thermal heat Rats (male) The enkephalinase inhibitor SCH-32615 injected bilaterally in the CEA induced antinociception (increased latencies) in the hot-plate test, but not the tail-flick test, and these effects were naloxone reversible Enkephalinase inhibitor in CEA is antinociceptive al-Rodhan, Chipkin, and Yaksh (1990)
CEA (CMA) BLA Morphine MOR Jump thresholds with footshock Rats (male) Morphine injections into the centromedial amygdala, but not the BLA, increased jump thresholds to footshock. No effects on activity were observed MOR agonist in centromedial amygdala is antinociceptive Rodgers (1977)
CEA, MEA Morphine, naloxone MOR Jump-flinch thresholds with footshock Rats (male) Morphine injections in CEA and MEA both increased thresholds for jumping/flinching in response to footshock, but these were only reversed by naloxone in the MEA MOR agonist in CEA and MEA is antinociceptive Rodgers and File (1979)
CEA, BLA Morphine, naloxone MOR Conditioned hypoalgesia in hot-plate and formalin tests of nociception Rats (male) Unilateral morphine injections into CEA, but not BLA decreased acquisition of hypoalgesia induced by prior hotplate exposure, in both hotplate and formalin-induced responses. Morphine in the CEA attenuated the expression of formalin-induced hypoalgesia, but not hotplate paw lick latencies Morphine in CEA impairs acquisition and retention of conditioned hypoalgesia Good and Westbrook (1995)
CEA Enkephalinase inhibitor RB101, morphine, methylnaloxonium MOR Tail-flick and vocalizations to tail shock Rats (male) Injections of methylnaloxonium into the CEA attenuated the systemic analgesic effects of both morphine and the enkephalinase inhibitor RB101 on motor response (tail-flick) and vocalizations (tail-shock vocalizations and after-discharge vocalization) with tail-shock MOR antagonist in CEA blocked the analgesic effects of morphine and an enkephalinase inhibitor Valverde, Fournie-Zaluski, Roques, and Maldonado (1996)
CEA nor-BNI, DYN KOR Stress (bright light exposure), morphine-induced hyperalgesia, paw-withdrawal thresholds in Randall-Selitto paw pressure test after capsaicin conditioning stimulus, DYN levels Rats (male) In rats with opiate-induced hyperalgesia, stress (bright light exposure), re-instated tactile allodynia and caused a loss of inhibitory control after capsaicin that was attenuated by nor-BNI injections in the right, but not left, CEA. DYN-A levels in the right CEA were also increased. These effects were only seen with the combination of morphine-induced hyperalgesia and stress Increased KOR activity in CEA is associated with nociceptive inhibitory control induced by morphine-induced hyperalgesia and stress Nation et al. (2018)
Basolateral amygdala
BLA Morphine MOR Tail-flick latencies to heat Rats (male) Bilateral morphine injections increased tail-flick latencies to radiant heat in anesthetized rats. The injection sites that were most effective were the BLA MOR agonist in BLA is antinociceptive Helmstetter, Bellgowan, and Tershner (1993)
BLA DAMGO, DPDPE, U50,488 MOR Tail-flick latencies to heat Rats (male) Bilateral DAMGO injections into BLA dose dependently increased tail-flick latencies to radiant heat in anesthetized rats. No effects of DPDPE (DOR) or U50,488H (KOR) were seen MOR agonist in BLA is antinociceptive Helmstetter, Bellgowan, and Poore (1995)
BLA DAMGO MOR Tail-flick latencies, HR Rats (male) DAMGO injected bilaterally in BLA decreased tail-flick latencies in anesthetized rats, but did not change HR. This effect was attenuated by decreasing activity in the vlPAG or RVM using lidocaine or electrolytic lesions MOR agonist in BLA is antinociceptive Helmstetter, Tershner, Poore, and Bellgowan (1998)
BLA DAMGO MOR Tail-flick latencies, HR Rats (male) DAMGO injected bilaterally in BLA increased tail-flick latencies. This effect was attenuated by injections of CTAP, but not naltriben, in the vlPAG MOR agonist in BLA is antinociceptive Tershner and Helmstetter (2000)
BLA DAMGO, CTAP, βFNA, naltrexone MOR Tail-flick latencies to heat Rats (male) DAMGO injected bilaterally in BLA increased tail-flick latencies. These effects were blocked by naltrexone and βFNA, but not CTAP. From injection autoradiograms, some parts of injection might have influenced IN or CLC MOR agonist in BLA is antinociceptive Shin and Helmstetter (2005)
BLA, MEA Morphine, naloxone MOR Tail-flick latencies to heat, RVM on and off cell activity Rats (male) Bilateral morphine injections in BLA increased tail-flick latencies with heat in a naloxone-reversible manner. Injections into the cortical nuclei had a smaller effect. Injections in CEA, MEA, LA had no effect. Injections of morphine in the BLA, cortical nuclei and MEA all influenced RVM on and off cell activity, including increasing off-cell firing and reducing on-cell firing MOR agonist in BLA is antinociceptive McGaraughty and Heinricher (2002)
BLA, MEA Morphine, naloxone MOR Tail-flick latencies to heat, RVM on and off cell activity Rats (male) Bilateral morphine injections in the BLA increased tail-flick latencies with heat. Injections in MEA had no effect on tail-flick latencies. Injections of morphine in the BLA and MEA increased off-cell firing and reduced on-cell firing in RVM. All of these effects were blocked by PAG lesions, suggesting antinociceptive effects of morphine in the BLA require projections through PAG to RVM MOR agonist in BLA is antinociceptive McGaraughty, Farr, and Heinricher (2004)
BLA Morphine, methylnaloxonium MOR Tail-shock induced spinal reflexes and vocalizations Rats (male) Bilateral morphine injections into the BLA increased thresholds for inducing vocalizations during tail-shock and vocalization after discharges, but not the thresholds for spinal motor reflexes, suggesting morphine attenuated the affective component of pain. Effects of morphine were blocked by the MOR selective antagonist methylnaloxonium and were specific to injection sites in the BLA MOR agonist in BLA is antinociceptive Nandigama and Borszcz (2003)
BLA Morphine, naloxone MOR Formalin-induced behaviors; glutamate release in BLA Rats (male) Morphine injections into the BLA blocked formalin-induced conditioned place aversion, but not formalin-induced nociceptive behaviors (licking/biting/flinching). Perfusion through the microdialysis probe also blocked formalin-induced increases in glutamate efflux in the BLA MOR agonist in BLA blocks formalin-induced conditioned place aversion and glutamate efflux Deyama et al. (2007)