Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Wednesday, July 13, 2011

Neuraxial analgesia & anaesthesia - A review

Let's first consider the basic pharmacological function of opioid analgesia:

1) Inhibition of Pain (Actual Relief)

Within the dorsal horn (Opioid analgesia occurs heavily here)

A-delta (Instant, rapid, sharp pain) fibers enter the posterior marginalis and the nucleus proprius

C fibers enter the substantia gelatinosa

These impulses are either inhibited from reaching the higher centers (thus never interpreted), or continue ascending upwards to the thalamus.

2) Increased Pain Tolerance (Blunting perception of pain with a sense of well being)

Sensory input which makes it succesfully to the brain will be interpreted as less distressing or perhaps obsolete; due to increased firing from the mesolimbic dopamine pathways to the nucleus accumbens (pleasure center of the brain) In essence; at the higher cortical levels, opioids simply alter one's interpretation or tolerance of the pain - "The pain is there but doesn't bother me".

Attacking Pain At Its Origin;

Considering specifically the efficacy of opioid-mediated analgesia at the spinal level, the spinal cord being a key point of our opioid receptor system, it is no surprise that administration of opioids by the direct intraspinal route has become standard practice. Originally performed in hospital anaesthesia settings and presently becoming commonplace in the outpatient field of supportive chronic pain therapy .

The spinal route offers administration of drugs directly to the central compartment avoiding many side effects common with systemic opioids - i.e. less sedation, respiratory depression & nausea. This is possible due to the minimal levels of opioid absorbed systemically by this route, and the specificity of the drug's action; in the spinal cord and primarily limited to the area of administration. Inevitably a portion of the administered opioid will follow the flow of CSF (spinal fluid) ascending to higher areas including the brain, however these levels are still very low compared to those seen with the non spinal routes.

Still one may ask; what it the use performing an invasive spinal when oral or IV agents will be eventually active centrally? - Simple; by administering the agent directly to one of their primary sites of action, highly direct, controlled, and effective analgesia can be achieved with the use of substantially smaller doses, and without pointlessly affecting other organs/tissues of the body. For instance, why bomb an entire building to kill one target rather than take aim directly at the target with a sharpshooter?

The idea is the targeting of nociception at the spinal level. More specifically targeting the ascending nociceptive pathways of the dorsal horn; home to vast concentration of pre and post synaptic opioid receptors. Opioids diffuse directly into the spinal cord dorsal region and activate mu, kappa, delta receptors; leading to an inhibition of of brain bound nociceptive impulse; while also increasing the flow of descending inhibitory impulse. These pathways are a major highway of sorts, with the opioid system serving as traffic lights; the northbound route is closed while the southbound route is busy with fast moving traffic.


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