Depression as a possible pain disorder: The role of opioids in relieving depression?

[nuke]

I stumbled upon this study recently:

Neuropeptides. 2009 Oct;43(5):341-53. Epub 2009 Aug 3.

The role of beta-endorphin in the pathophysiology of major depression.

Hegadoren KM, O'Donnell T, Lanius R, Coupland NJ, Lacaze-Masmonteil N.

Faculty of Nursing, University of Alberta, Edmonton, AB, Canada T6G 2G3. [email protected]

A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta-END in the pathophysiology of MDD must be paralleled by consensus building within the research community around the heterogeneity inherent in mood disorders, standardization of experimental protocols, improved discrimination of POMC products in analytical techniques and consistent attention paid to important confounds like age and gender.

which includes this section:

5. Serotonin, depression and b-END
As previously mentioned, one of the major etiological theories
of depression involves monoamine systems, in particular the
5-HT system. Animal studies support links between b-END and
5-HT systems, yet few human studies exist that have investigated
this relationship. Microdialysis studies on rats have demonstrated
dose-dependent increases in b-END levels in the diasylate from the
arcuate nuclei in response to 5-HT (Zangen et al., 1999). Increases
in b-END levels were also seen in the nucleus accumbens, but only
at the highest doses of 5-HT. Chemical lesioning with 5,7-dihydroxytryptomine
decreased b-END levels and adding fluoxetine to
the perfusion media increased b-END levels in both regions. Agonists
at 5-HT1 and 5-HT2 receptors also increased plasma b-END
immunoreactivity in rats (Bagdy et al., 1990). However, plasma
b-END levels did not change in response to fenfluramine, an indirect
5-HT agonist in a small sample of depressed subjects (Weizman
et al., 1988). Acute administration of 5-hydroxytryptamine
attenuated the suppression of b-END in response to dexamethasone
(DEX) in subjects with MDD (Maes et al., 1996). Despite the
paucity of studies, the extensive 5-HT involvement in hypothalamic
function and the concentration of b-END-releasing neurons
in the hypothalamus would suggest multiple potential interactive
links between the two.

The concept is really kind of simple: The patient who has chronic pain is often depressed. Emotional pain is known to cause or to worsen actual physical in the patient. So would it be possible by the use of a partial mu-opioid agonist or some system that modulates endogenous opioid peptide levels (catabolic inhibitors?) chronically may achieve remission from depression is some patients?

 

[pofacedhoe]

tramadol is the first antidepressant that worked for me and i'm acctually fine now i'm off it. my social skills have improved and i can take rejection now in a way that i could never before.

i just dont find life so offensive

http://latimesblogs.latimes.com/boo...nd-physical-pain-linked-by-a-common-gene.html

i dont have access to the study

 

[seep]

Is this derivative of the old MENTAL PAIN HYPOTHESIS OF DEPRESSION, which never seemed to gain much traction? I'm too lazy to log into my U3W account right now and get the full text of this paper and the 1986 one that precedes it:

NSFW:

1. Clin Neuropharmacol. 1989;12 Suppl 1:S4-10.

Trazodone: from the mental pain to the "dys-stress" hypothesis of depression.

Silvestrini B.

Institute of Pharmacology and Pharmacognosy, University of Rome La Sapienza,
Italy.

Trazodone was developed according to the mental pain hypothesis, which was
postulated from studying patients and which proposes that depression is
associated with a decreased pain threshold. Trazodone is devoid of the typical
aminergic properties of tricyclics and monoamine oxidase inhibitors. Its
preeminent effects are increased pain threshold and alpha-adrenergic blockade.
The "dys-stress" hypothesis maintains the concept of the decreased pain threshold
in depression, but attributes it to a pathology of the stress response. Whereas
physiologically this response produces various effects, including analgesia and
alertness that improve the mental and physical performance, in some individuals
it is impaired. Abnormalities of the stress response are proposed to be a
predisposing or pathogenetic factor for depression and other conditions.
According to the "dys-stress" hypothesis, the alpha-adrenergic blockade produced
by trazodone and its congeners would also be implicated in its antidepressant
activity, as well as its side effects and preferential uses in depressive states
associated with adrenergic hyperactivity.

PMID: 2568177 [PubMed - indexed for MEDLINE]

For whatever it's worth, I've been experiencing fantastic mood-lifting effects since experimenting with daily metformin. I initially ingested it by accident, thinking it was bupropion, and noticed a mild, controlled-release-opiate sensation. After doing a tiny bit of digging, I found a link b/w metformin and elevated beta-endorphin:

1. Horm Metab Res. 2006 Feb;38(2):106-11.

Metformin increases insulin sensitivity and plasma beta-endorphin in human subjects.

Ou HY, Cheng JT, Yu EH, Wu TJ.
The Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, College of Medicine, Tainan, Taiwan.

Metformin has been widely used in clinical type 2 diabetes treatment and prevention. The present study was designed to explore the effect on people with a sedentary lifestyle at therapeutic doses. Twenty-two physically-inactive volunteers with normal glucose tolerance were studied. Escalating doses of metformin in low-dose (250 mg), intermediate-dose (500 mg), and high-dose (750 mg) treatment three times per day were administrated into each subject over a three-week treatment period. Fasting plasma glucose, A1C, HOMA-IR for insulin resistance, lipid profile, and plasma beta-endorphin-like immunoreactivity (BER) were measured before treatment and weekly at the and of each dosing period. Metformin significantly reduced fasting plasma glucose and HOMA-IR in healthy humans after receiving this treatment at therapeutic doses including low-dose (5%, 17 %), intermediate-dose (6 %, 25%) and high-dose treatment (6 %, 21 %). Plasma BER was also increased from 135.46 +/- 61.73 pg/ml to 137.52 +/- 66.11 pg/ml by low-dosing (p = 0.39), to 139.17 +/- 64.08 pg/ml by intermediate-dosing (p = 0.32), and to 149.59 +/- 63.32 pg/ml by high-dosing (p < 0.05). Also, serum cholesterol decreased significantly using metformin at therapeutic doses including low-dose (4 %), intermediate-dose (8 %) and high-dose treatment (7 %). However, metformin failed to modify levels of serum HDL-cholesterol and C-reactive protein (CRP) in healthy subjects. Also, the reduction of serum cholesterol by metformin did not correlate to the increase in insulin sensitivity. In conclusion, metformin causes a significant parallel increase in insulin sensitivity and plasma beta-endorphin level in human subjects.

PMID: 16523411 [PubMed - indexed for MEDLINE]