Comparison of subjective and objective analgesic effects of intravenous and intrathecal morphine in chronic pain patients by heat beam dolorimetry

Abstract

The pain tolerance latencies of 10 chronic pain patients were evaluated by heat beam dolorimetry (stimulus intensity 15.33 mW.cm-2.sec-1) prior to and following administration of morphine by intrathecal (n = 5) or intravenous (n = 5) routes. Patients not undergoing opiate withdrawal evinced increased baseline pain tolerance latencies prior to drug administration compared with normal volunteers. Two patients undergoing the opiate withdrawal syndrome at the time of test experienced reduced pain tolerance latencies compared with normal volunteers, most probably corresponding to the hyperesthesia symptom of the syndrome. Intravenous morphine infusion (30 mg) induced a time-dependent increase in cutaneous pain tolerance with peak effect occurring 1-2 h after administration. This persisted for up to 4 h and thereafter declined. The time course of subjective pain self-report by visual pain analog scale (VPAS) measurements corresponded to the time course of increasing cutaneous pain tolerance latency assessed by dolorimetry. Pain self-reports following intrathecal morphine infusion (2.25 or 1 mg) followed a similar though slower onset to that reported by patients receiving intravenous morphine and was of lesser degree. In contrast, heat beam dolorimetric evidence of increased cutaneous pain tolerance (which was of lesser degree than following i.v. morphine) did not reach its maximum during the 4 h measuring period. A dissociation was noted therefore between the self-reported relief of endogenous pain and dolorimetrically measured cutaneous analgesia following intrathecal morphine administration. Linear regression correlation analysis characterized this phenomenon as a positive correlation between cutaneous pain tolerance and pain relief self-report following intravenous morphine infusion and a negative correlation following intrathecal administration. We propose that the phenomenon may be due to intrathecal morphine acting via two separate compartments: one spinal and one supraspinal.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid-Induced Hyperalgesia and Incisional Pain

“…Our animal data indicate that the excess hyperalgesia and allodynia resulting from OIH can be eliminated simply by maintaining preincisional opioid levels. Given that OIH can occur in humans (5,6,24), it would seem prudent to remain cognizant of the potential consequences of rapid downward changes in opioid doses in the perioperative setting.…”

“…This manifestation of OIH is not limited to the well-described pain complaints of those who abuse drugs and subsequently undergo opioid withdrawal. There are now reports documenting spontaneous pain, allodynia, and thermal hyperalgesia in humans after reductions in dosage or abrupt cessation of opioids administered for therapeutic purposes (5,6). Likewise, sudden cessation of intrathecal morphine delivery because of catheter malfunction can lead to a state of allodynia to mechanical stimuli (light touch) that resolves on resumption of opioid administration (7).…”

Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study

“…48,89 Subsequent work confirmed that the severity of withdrawal hyperalgesia increases with intermittent or naloxone-interrupted opioid dosing 40,61,62 and that its development can be prevented by N-methyl-D-aspartate (NMDA) receptor antagonism, 5,6,21,22,57,61 suggesting that it is not unlike the hyperalgesia of neuropathic origin. 65,66,71 Although evidence for 1,15,17,18,63,84 and implications of 60 opioid withdrawal hyperalgesia on clinical pain states have not been ignored in this body of work, its presence has yet to be empirically evaluated in opioidexposed but otherwise healthy humans.An important and well-described experimental model for studying the clinical phenomenon of opioid withdrawal in humans is the induction of acute opioid physical dependence (APD). In this paradigm, healthy nonopioid-dependent subjects pretreated with a single large dose of opioid agonist (typically morphine sulfate [MS] 10 to 18 mg/70 kg) and challenged 4 to 6 hours later with a large dose of opioid antagonist (typically 10 mg/kg naloxone [NX] intramuscular [IM] or intravenous [IV]) exhibit not only a reversal of agonist effects but a true opioid withdrawal syndrome.…”

“…48, 89 Subsequent work confirmed that the severity of withdrawal hyperalgesia increases with intermittent or naloxone-interrupted opioid dosing 40, 61,62 and that its development can be prevented by N-methyl-D-aspartate (NMDA) receptor antagonism, 5,6,21,22,57,61 suggesting that it is not unlike the hyperalgesia of neuropathic origin. 65,66,71 Although evidence for 1,15,17,18,63,84 and implications of 60 opioid withdrawal hyperalgesia on clinical pain states have not been ignored in this body of work, its presence has yet to be empirically evaluated in opioidexposed but otherwise healthy humans.…”

Current and Future Issues in the development of spinal agents for the management of pain

“…Intrathecal (superficially applied) agents must diffuse into the parenchyma to reach these target sites. As diffusion from the surface to the presumed site of action is a time-dependent process that is proportional to distance, it is interesting to note that all things being equal for a given drug such as morphine, the time of onset is fastest in the mouse (2-3min) [444] and proportionally more delayed in larger animals (30 min in cat and dog) [445][446][447] to >1 hr in humans [448,449]. Importantly, several variables define the ability of a drug to diffuse into tissue.…”