Relative opioid potency in humans vs. test animals

[Everlasting Reign]

There are several commonly used laboratory animals on which opioid potency is tested, the most common being the rat and mouse, and also a further variety of different tests and sub-tests performed on these test animals, such as the mouse hot plate test, the rat tail flick test, the writhing test, etc.

Is there a general rule or consensus that one or more of these methods gives a best approximation of analgesic potency in humans? Such tests performed on the rat seems to give a uniformly higher rating of potency than those on the mouse, e.g. the potency of fentanyl in the rat according to some tests is around 250x morphine, but tests in the mouse seem to return values closer to the generally accepted potency of fentanyl in man, approx. 80-100x morphine.

 

[sekio]

Rat and mouse tests are usually a ballpark figure. It's hard to scale results from a tiny mammal to a much bigger one with a more advanced liver.

 

[negrogesic]

The results from nox-stim animal nociception tests are certainly valuable, but the data must be taken with a grain of salt. Human equianalgesic opioid charts can vary significantly, and ones based heavily on animal nociception tests are rather poor.

While we do have powerful technologies to assess opioid potencies (QSAR, r-labels, etc), there is no simple 'rule' when it comes to the clinical use of opioids in the treatment of the complex arena of human 'pain'.

This is not to say that binding assays are far off or irrelevant, as these metrics are invaluable (particularly when dealing with the ultra-potent synthetics).

In my specific sub-spec of anesthesiology (card-thor), our concern is generally not about palliative medicine, but if you want a realistic equianalgesic estimate for a particular opioid, list your sex, weight, relevant med-histories etc, and I can give you a better idea. If you are using opioids for recreation in the absence of pain, please indicate accordingly. Equianalgesic estimates are a bit different than qualitative and quantitative 'equiahighogesic" figure.

 

[Sturnam]

Well, for one, rats at least are hardy creatures. You can do a pretty major surgery on them (brain cannulation, intrathecal catheter, jugular vein catheter, etc) and have them be up and running the next day. I doubt any human could do that.

So generally, you have to induce pain via several ways. Thermal and mechanical are two different types of input for pain, and can have differing strengths, depending on the injury. There's also neuropathic pain to consider. Each of these will be differentially affected by morphine. For instance, the ED50 for thermal pain could be 0.5 mg/kg, but for mechanical could be 1.5 mg/kg. And neuropathic pain is usually higher than both of those, say 3 mg/kg.

Also, yeah rats have huge livers, which means that they transform and excrete exogenous substances very rapidly.

In essence, the type of test used determine analgesic efficacy. As to which test is 'best' for approximating human pain, well, that is anyone's guess.

 

[negrogesic]

http://m.pharmrev.aspetjournals.org/content/53/4/597.full#title57

 

[fastandbulbous]

Opioids have varying effect on different species, it's all down to the way their metabolism evolved. For instance, dogs are much more tolerant of opioids than humans (as are several species) such that etorphine can be used on them for surgical proceedures; now etorphine is so potent in humans that a vet cannot buy Immobilon (etorphine for injection) without getting a vial of cyprenorphine (the specific antagonist), which must be kept with the immobilon at all times (there is a report of a vet who was using immobilon on seals, who had to be whisked off to an A&E dept because he accidentally stuck himself with an immobilon dart and had forgotton the antaghonist. In the end, it was discovered his OD was brought about by the volume of soln in the needle, not the barrel, just the volume of the inside of the needle ie a few microlitres! That amount would hardly touch a seal)

Some species are way too sensitive for most opioids to be used medicinally, such as morphine in cats because the analgesic dose is just slightly less than that required to cause spinal clonic-tonic convulsions