Endorphins: Naloxone Fails to Alter Experimental Pain or Mood in Humans

Grevert, Priscilla; Goldstein, Avram

doi:10.1126/science.343250

Cited by 180 publications

(57 citation statements)

References 16 publications

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“…This hyperalgesic effect has been demonstrated in humans [40] and animals [41] supporting the notion that naloxone antagonizes a tonic, opioid mediated inhibition of nociception. The intraseptal injection of morphine and pentazocine also had no effect on pain threshold after septal lesions, however our study indicates that interaseptal injection of naloxone produces analgesia.…”

Section: Discussionsupporting

confidence: 53%

Modulation of Pain by Naloxone and a Possible Role of Neurotransmitters with Selective Lesion of Septal Nuclei

Somade¹,

Brid²

2015

J Spine

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Septum occupies a strategic position in limbic system and has been implicated in variety of behaviors. Present study was designed to evaluate the role of medial septum in modulation of pain and explore the role of neurotransmitters.The present study was divided in two parts in first part the tail flick latencies were observed in rats with septal lesions and compared with sham operated ones. While in the second part, the effect of intraseptal injections of neurotransmitters and naloxone on tail flick latencies ofcannulated rats was recorded after intraseptal lesions.It was observed that the septal lesions decrease pain threshold. The interaseptal injection of Acetylcholine (5 µg to 20 µg) and Naloxone (5 µg to 20 µg) increases pain threshold. While the Interaseptal injection of Noradrenaline and Scopolamine decreases pain threshold.The findings of the present study suggest that septum may be involved in modulation of pain. The neurotransmitters like Acetylcholine, Noradrenaline and opioid peptides may have an individual or collective role to play in the observed pain modulation.

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Section: Discussionsupporting

confidence: 53%

Modulation of Pain by Naloxone and a Possible Role of Neurotransmitters with Selective Lesion of Septal Nuclei

Somade¹,

Brid²

2015

J Spine

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“…The effects of µ-opioid receptor blockade on experimental pain are inconsistent, with reports of pain increasing after naloxone administration (Buchsbaum et al, 1983;Borras et al, 2004), not changing (El-Sobky et al, 1976;Grevert and Goldstein, 1978), or decreasing (Stacher et al, 1988;Al'Absi et al, 2004). This inconsistency may be due to individual differences in pain sensitivity (Buchsbaum et al, 1983) or could be dose-related.…”

Section: Discussionmentioning

confidence: 99%

Negative affect, pain and sex: The role of endogenous opioids

Frew

Drummond

2007

Pain

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Opioid neurotransmission modulates pain and negative affect during psychological stress.To determine whether these effects differ between men and women, the opioid receptor antagonist naltrexone or placebo was administered double-blind to 21 men and 22 women before they completed 30 minutes of difficult mental arithmetic. To heighten negative affect, participants received seven moderately noxious electric shocks during the math task, which were believed to be contingent upon performance. Before and after the math task, participants rated pain intensity and unpleasantness while their left hand was immersed in 2 o C water for up to 4 minutes. Anxiety, discouragement and anger were also rated before, during and after the math task. Tolerance of cold-induced pain was greater in men, whereas discouragement during the math task was greater in women. Opioid blockade did not influence ratings of negative affect, which increased in line with the intensity and unpleasantness of shock-induced pain. The intensity and unpleasantness of cold-induced pain increased after the math task only in women administered naltrexone.Within the naltrexone condition, pain ratings increased most in the most discouraged subjects. However, this relationship was absent in placebo recipients, implying that the hyperalgesic effect of psychological distress was tempered by opioid release. Greater stress-evoked discouragement in women than men may explain why cold-induced pain increased after the math task only in women administered naltrexone.

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“…In human research, µ-opioid receptor blockade antagonized stress-induced analgesia evoked by noxious electric shocks [47,48], immersion of a limb in ice-water [28,40], the perception of failure on a difficult cognitive task [2,3,20], a combat video shown to Vietnam veterans with post-traumatic stress disorder [38], and a first-time parachute jump [27]. Effects of µ-opioid receptor blockade on experimental pain are more variable [16,23,40], possibly because of individual differences in sensitivity to or release of opioid peptides. For example, naloxone augments shock-induced pain and cortical evoked potentials in pain-tolerant people, but inhibits pain and cortical evoked potentials in pain-sensitive people [10].…”

Section: Stress-induced Analgesiamentioning

confidence: 99%

Stress-evoked opioid release inhibits pain in major depressive disorder

Frew

Drummond

2008

Pain

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To determine whether stress-evoked release of endogenous opioids might account for hypoalgesia in major depressive disorder (MDD), the µ-opioid antagonist naltrexone (50 mg) or placebo was administered double-blind to 24 participants with MDD and to 31 non-depressed controls. Eighty minutes later participants completed a painful foot cold pressor test and, after a 5-minute interval, began a 25-minute arithmetic task interspersed with painful electric shocks. Ten minutes later participants completed a second cold pressor test. Negative affect was greater in participants with MDD than in non-depressed controls throughout the experiment, and increased significantly in both groups during mental arithmetic. Before the math task, naltrexone unmasked direct linear relationships between severity of depression, negative affect while resting quietly, and cold-induced pain in participants with MDD. In contrast, facilitatory effects of naltrexone on cold-and shock-induced pain were greatest in controls with the lowest depression scores. Naltrexone strengthened the relationship between negative affect and shock-induced pain during the math task, particularly in the depressed group, and heightened anxiety in both groups toward the end of the task. Thus, µ-opioid activity apparently masked a positive association between negative affect and pain in the most distressed participants. These findings suggest that psychological distress inhibits pain via stress-evoked release of opioid peptides in severe cases of MDD. In addition, tonic endogenous opioid neurotransmission could inhibit depressive symptoms and pain in people with low depression scores.

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Endorphins: Naloxone Fails to Alter Experimental Pain or Mood in Humans

Cited by 180 publications

References 16 publications

Modulation of Pain by Naloxone and a Possible Role of Neurotransmitters with Selective Lesion of Septal Nuclei

Modulation of Pain by Naloxone and a Possible Role of Neurotransmitters with Selective Lesion of Septal Nuclei

Negative affect, pain and sex: The role of endogenous opioids

Stress-evoked opioid release inhibits pain in major depressive disorder

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