Table 5.
Schematic overview of studies involving morphine in human experimental pain models
| Reference | Dose | Model | Findings | |
|---|---|---|---|---|
| Acute models | [96] (n= 13) | 0.02 mg kg−1 iv | Heat skin stimulation VAS (affective and sensory) (37, 49 and 51°C) | Affective or sensory responses ↔ |
| [102] (n= 10) | 0.08 mg kg−1 iv | Heat skin stimulation PDT, PTT (0.5°°C s−1) Deep pressure PDT Ischemic pain PDT, PTT | All thresholds were increased | |
| [81] (n= 12) | 30 mg p.o. | Heat skin stimulation PDT, PTT (2°C s−1), cold, Pressure algometry PTT (finger pulp) Electrical skin stimulation (single and repeated) Cold pressor test VAS, peak pain, mean pain, AUCVAS | Pain to pressure, cold pressor test, single and repeated electrical stimulation were decreased Heat pain ↔ | |
| [37] (n= 10) | 4 mg epidural | Heat and cold skin stimulation detection threshold, PDT, PTT (1 and 2°C s−1) Electrical skin stimulation PDT, VAS to 1 ms stimulation Pressure algometry PDT, PTT, moderate pain to 20 ms stimulation (toe nail) Short lasting radiant heat VAS (argon laser, 200 ms) | Cold detection threshold ↔ Warmth detection threshold, PDT, PTT to heat, pressure, and electrical stimulation ↑ (PTT>PDT) VAS after short lasting radiant pain ↓ Short lasting pain (1 and 20 ms) to mechanical and electrical stimulation ↔ | |
| [83] (n= 30) | 0.15 mg kg−1 iv | Short lasting radiant heat warmth detection threshold, pinprick PDT (argon laser, 200 ms) | Warmth detection or pinprick PDT ↔ | |
| [86] (n= 7) | 10 mg iv | Intra cutaneous electrical stimulation VAS, evoked brain potentials and frequency analysis | Amplitude of evoked potentials and VAS↓ EEG frequency spectrum ↔ | |
| [51] (n= 10) | 0.142 mg kg−1 iv | Electrical tooth stimulation evoked brain potential, subjective pain report (6 point scale) | Amplitude of evoked potentials and pain score ↓ | |
| [48] (n= 16) | 0.14 and 0.28 mg kg−1 iv | Intramuscular injection of hypertonic saline AUCVASIntramuscular electrical stimulation PDT, AUCVAS to suprathreshold stimulation for 10 s | High dose: All parameters affected Low dose: All parameters ↔ | |
| [53] (n= 15) | 0.1 mg kg−1 iv | Cutaneous and intramuscular electrical stimulation PDT, AUCVAS to suprathreshold stimulation for 10 s Intramuscular injection of hypertonic saline AUCVAS | PDT to intramuscular electrical stimulation ↑ PDT to electrical skin stimulation, AUCVAS after suprathreshold stimulation and hypertonic saline ↔ | |
| [86] (n= 12) | 60 mg extended release orally | Cold pressor test PTT | PTT ↑ | |
| [87] | 0.5 mg kg−1 orally | Cold pressor test PDT, PTT, VAS | Latency to onset of pain and PTT ↑ | |
| [90] (n= 34) | 0.5 mg kg−1 orally | Cold pressor test PDT, PTT, VAS | PDT and PTT ↑ VAS ↓ | |
| [89] (n= 19) | 0.1 mg kg−1 iv | Ischemic pain VAS (summated) | VAS ↓ | |
| [5] (n= 24) | 30 mg orally | Heat skin stimulation PTT (2°C/s) Deep pressure PTT Pinching PTT Cutaneous and intramuscular electrical stimulation PTT Oesophageal distension and electrical pain PTT Oesophageal heat pain PDT | Oesophageal heat pain ↔ The remaining pain thresholds parameters ↓ | |
| [95] (n= 10) | 100 ng ml−1 iv | Electrical skin stimulation PDT, PTT | PDT and PTT ↑ | |
| [106] (n= 28) | 20 mg or 30 mg single dose orally | Cold pressor test AUCVAS, peak pain, discomfort (VAS) Heat skin stimulation and deep pressure PDT | Peak pain and discomfort in cold pressor test ↓ AUCVAS and heat PDT and PTT ↔ Pressure PTT ↓ whereas PDT ↔ | |
| [91] (n= 9) | 0.1 mg kg−1 iv | Ischaemic pain AUCVAS | AUCVAS↓ | |
| [97] (n= 47) | 0.04–0.08 mg kg−1 iv | Heat skin stimulation VAS (sensory and affective dimension) to graded temperatures and VAS to brief pulses (first and second pain) | Dose < 0.06: VAS (affective) ↓, VAS (sensory) ↔ Dose > 0.06: VAS (affective and sensory and first and second pain) ↓ | |
| [92] (n= 45) | 10 mg 70 kg−1 iv | Ischaemic pain PTT | PTT ↑ | |
| [84] (n= 10) | 4 mg injected perineurally to ulnar nerve and epidurally | Short lasting radiant heat PDT and warmth detection threshold), evoked brain potentials (argon laser, 200 ms) | PDT and warmth detection threshold ↑ Amplitude of evoked brain potentials ↓ Latencies of evoked brain potentials↑ after perineural administration | |
| Models inducing hyperalgesia | [57] (n= 16) | 15 and 30 ng ml−1 measured at steady state | Burn injury PDT to pinprick in injured skin, area of secondary HA to pinprick Repeated pinprick AUCVASContinuous electrical skin stimulation PDT to pinprick, area of secondary HA to pinprick, repeated pinprick (AUCVAS) | Only the high dose had significant effect. Continuous electrical skin stimulation: PDT ↑ and area of HA↓ Burn injury and repeated pinprick: no parameters were significantly affected |
| [94] (n= 11) | 10 µg kg−1 min−1 for 45 min iv | Burn injury PDT to pinprick in injured skin, area of secondary HA to pinprick Repeated pinprick AUCVAS | No parameters were affected | |
| [41] (n= 12) | 0.15 mg kg−1 iv | Burn injury heat and cold detection threshold and PDT in primary and secondary HA area (1°C/s), area of secondary HA to pinprick, detection threshold to pinprick, appearance of wind-up like pain to repeated pinprick stimulation | No parameters were affected | |
| [93] (n= 12) | 2 mg sub-cutaneously | Burn injury, PDT to heat (1°C s−1) and deep pressure | Heat PDT ↑ Mechanical PDT ↑ | |
| [42] (n= 12) | 40 ml 0.01% iv | Ultraviolet (UV-B) radiation PDT to heat VAS to mechanical impact | Heat PDT ↑ VAS to mechanical impact ↔ | |
| [95] (n= 10) | 100 ng ml−1 iv | Freeze lesion PDT to pinprick Concentric and eccentric muscle contraction VAS | PDT to prinptick ↓ Muscle pain intensity ↔ |
In the column ‘model’ the method for pain assessment is normal font, and the method for pain induction is bolded. Abbreviations: pain detection threshold (PDT), pain tolerance threshold (PTT), area under curve (AUC), visual analogue scale score (VAS), hyperalgesia (HA).