As Dubious notes, this study has been around for a while, 2006 to be specific. I suspect it's making the rounds now because for some reason it was featured on the RSDSA homepage a week ago.
*
However, we are well-served to have this raised again by Sandra, because it's an important facet of pain medications with which we all should be familiar, the concept that we can be on large enough doses of opioids that they not only become essentially useless but they ultimately reinforce and strengthen what is already CNS generated pain. For the quick treatment on Wikipedia, see,
http://en.wikipedia.org/wiki/Opioid-...d_hyperalgesia
But just as importantly, there are a number of solutions other than "detoxification." In fact, there is evidence that a complete detox may well be "sub-optimal." See, Reduced cold pain tolerance in chronic pain patients following opioid detoxification, Younger J, Barelka P, Carroll I, Kaplan K, Chu L, Prasad R, Gaeta R, Mackey S.,
Pain Med. 2008 Nov;9(8):1158-63. Epub 2008 Jun 18, FREE FULL TEXT @
http://www.ncbi.nlm.nih.gov/pmc/arti...ihms140159.pdf
Abstract
OBJECTIVE: One potential consequence of chronic opioid analgesic administration is a paradoxical increase of pain sensitivity over time. Little scientific attention has been given to how cessation of opioid medication affects the hyperalgesic state. In this study, we examined the effects of opioid tapering on pain sensitivity in chronic pain patients.
DESIGN: Twelve chronic pain patients on long-term opioid analgesic treatment were observed in a 7- to 14-day inpatient pain rehabilitation program, with cold pain tolerance assessed at admission and discharge. The majority of participants were completely withdrawn from their opioids during their stay.
OUTCOME MEASURES: We hypothesized that those patients with the greatest reduction in daily opioid use would show the greatest increases in pain tolerance, as assessed by a cold pressor task.
RESULTS: A linear regression revealed that the amount of opioid medication withdrawn was a significant predictor of pain tolerance changes, but not in the direction hypothesized. Greater opioid reduction was associated with decreased pain tolerance. This reduction of pain tolerance was not associated with opioid withdrawal symptoms or changes in general pain.
CONCLUSIONS: These findings suggest that the withdrawal of opioids in a chronic pain sample leads to an acute increase in pain sensitivity. [Emphasis added.]
PMID: 18564998 [PubMed - indexed for MEDLINE] PMCID: PMC2751584
http://www.ncbi.nlm.nih.gov/pubmed/18564998
The good news is that there are a number of fixes for the problem, including not only that old favorite, opioid rotation, but now there are actual or potential options of adding to the opioid another compound, whether it’s (1) a so-called “NMDA receptor antagonist,” which could be as simple as the over-the-counter cough suppressant dextromethorphan, in order to block pain processing from the spinal column to the brain, or (2) the most minute amount (in millionths of a gram) of an opioid blocker which has the paradoxical effect of increasing (potentiating) the analgesic qualities of the narcotic while reducing the total amount taken, and therefore the side effects.
As to the use of NDMA receptor antagonists, see, generally, Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats, Haugan F, Rygh LJ, Tjølsen A, Acta Anaesthesiol Scand. 2008 May;52(5):681-7:
Abstract
BACKGROUND: Long-term opioid treatment is associated with the development of hyperalgesia. In a rat model we wanted to study if chronic opioid treatment changed the induction and maintenance of spinal long-term potentiation (LTP), a form of hyperexcitability in the spinal cord. We also wanted to investigate if the clinically available NMDA receptor antagonist ketamine inhibited the effect of chronic opioid treatment on LTP.
METHODS: The animals were randomized into four groups (saline, morphine 20 mg/kg/day, ketamine 20 mg/kg/day, morphine 20 mg/kg/day and ketamine 20 mg/kg/day). Drugs were given as continuous subcutaneous infusions by means of osmotic minipumps. After 7 days of treatment and during ongoing treatment single unit extracellular recordings were made from the lumbar deep dorsal horn under urethane anesthesia. Single electrical stimuli were applied to the sciatic nerve, and the C-fiber evoked responses of WDR neurons were recorded before and during 3 h following low frequency (3 Hz) electrical conditioning stimulation.
RESULTS: The potentiation of C-fiber evoked responses by conditioning stimulation was significantly increased in the morphine-treated group compared to the saline group, while there was no significant difference between the saline, the ketamine and the morphine/ketamine groups. The potentiated responses in the morphine/ketamine group were significantly reduced compared to the morphine group (P=0.01).
CONCLUSION: Our results indicate that animals treated with long-term opioid show amplification of stimulus-induced central sensitisation compared to opioid naïve animals. Ketamine inhibited the morphine-induced enhancement of LTP, supporting the role of ketamine in prevention of opioid induced hyperalgesia.
PMID: 18419722 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18419722
And, with respect to the effect of NDMA receptor antagonists, it's not just ketamine, magnesium appears to have a similar effect. See, e.g., Magnesium modifies fentanyl-induced local antinociception and hyperalgesia, Mert T, Gunes Y, Ozcengiz D, Gunay I,
Naunyn Schmiedebergs Arch Pharmacol. 2009 Nov;380(5):415-20. Epub 2009 Aug 21:
Abstract
Fentanyl-induced hyperalgesia and antinociception after systemic administration has been shown in previous clinical and experimental studies. However, there is very little evidence regarding the local possible effects of fentanyl. The purpose of this study was to assess whether local (intraplantar) fentanyl administration can produce antinociception and hyperalgesia. In addition, we examined the effects of magnesium, N-methyl-D-aspartate receptor antagonist, on possible changes produced by fentanyl. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive actions. Intraplantar administration of fentanyl caused time and dose-dependent increase in the paw withdrawal latencies (antinociception). Coinjection of magnesium with fentanyl markedly enhanced the antinociception. However, fentanyl also markedly decreased paw withdrawal latencies 24 h after intraplantar administration (hyperalgesia). In the presence of magnesium, hyperalgesia after fentanyl administration was not observed. Consequently, following the fentanyl administration, local hyperalgesia after antinociception is a negative effect in pain treatment. Magnesium may not only prevent the hyperalgesia but also enhance antinociceptive effect of fentanyl. [Emphasis added.]
PMID: 19697012 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19697012
Having said that, although the combination opioids with trace amounts of an opioid block is a proven concept in the lab, and drug companies are falling all over themselves to be the first to gain FDA approval of their particular combination, none have made the grade so far. And although a number of people on the forum have found that one such drug - marketed to assist in the withdrawal from narcotic dependency/addiction - has been of real help to them, my pain mngt. doc hasn’t found it helpful in treating pain patients and so doesn’t prescribe it. (Search the forum under "Suboxone" and stay tuned for further developments.)
The bottom line is that no one should be resigning themselves to a life of bearing up under the weight of chronic pain, unless and until you’ve fully explored the issue of hyperalgesia and your options for dealing with it, with a good pain physician.
I hope this is helpful.
Mike
* Why I'm not sure, but there are two more articles up there now that were published in 2004 and 2009, respectively, and in the case of one of them, Carroll I, Clark JD, Mackey S, Sympathetic Block with Botulinum Toxin to Treat Complex Regional Pain Syndrome,
Ann Neurol. 2009;65:348-351, as recently as a couple of weeks ago, it wasn't on the RSDSA site and was only available through PubMed Central at
http://www.ncbi.nlm.nih.gov/pmc/arti...8/?tool=pubmed