Table 4. ʻSensitizingʼ Test Paradigms: Demographics and Drugs.
| [Ref.] First Author | N | Male/Female | Age (yr) | Drug | Dose | Administration | Additional drugs § |
|---|---|---|---|---|---|---|---|
| ʻSENSITIZINGʼ TEST PARADIGMS | |||||||
| Secondary Hyperalgesia Models | |||||||
| [26] Mikkelsen S | 23 | 23/0 | NR | Nx | B: 0.8 mg/15 min + 0.4 mg/h | i.v. | Ketamine |
| [27] Brennum J | 24 | 24/0 | 24; Range: 20–31 | Nx | B: 0.4 mg; B: 10 mg | i.v. | - |
| [28] Koppert W | 13 | 13/0 | 31 ± 5 | Nx | B: 10 microg/kg | i.v. | Remifentanil |
| [29] Koppert W | 15 | 12/3 | 29 ± 6 | Nx | B: 0.05, 0.5, and 5.0 microg/kg; TCI: 0.16, 1.6 and 16 microg/kg | i.v. | - |
| [30] Chu FL | 9 | 9/0 | 30 ± 9 | Nx | B: 0.1 mg/kg | i.v. | Remifentanil |
| [31] Pereira MP | 22 | 11/1 | F: 23 ± 1; M: 25 ± 2 | Nx | B: 21 microg/kg | i.v. | - |
| Summation Models | |||||||
| [32] Benedetti F | 173 | 90/83 | A | Nx | B: 0.14 mg/kg | i.v. | Capsaicin injection |
| [33] Price DD | 14 A | 0/14 | Mean: 46 | Nx | B: 0.8 mg | i.v. | Fentanyl |
| ʻPainʼ Models | |||||||
| Capsaicin: | |||||||
| [34] Graven-Nielsen | 15 | 15/0 | Mean: 24; Range: 21–31 | Nx | I: 0.8 mg /15 min + 0.5 mg /75 min | i.v. | Capsaicin injection |
| Capsaicin & heat: | |||||||
| [35] Drummond PD | 14 | 7/7 | Mean: 22 ± 6 SD | Nx | ITP: 0.5 mM | ITP | Capsaicin topical |
| [36] Anderson WS | 9 | 5/4 | Mean: 29 ± 5 SD | Nx | B: 0.1 mg/kg | i.v. | Capsaicin topical |
| Comb. modalities, others: | |||||||
| [37] Grevert P | 30 | 15/15 | NR | Nx | B: 1 mg/2 mg # ; B: 10 mg | i.v. | - |
| [38] McCubbin JA | 16 | 16/0 | Range: 18–24 | Nx | I: 8 mg | i.v. | - |
| [39] Stacher G | 24 | 12/12 | Range: 19–33 | Nx | I: 5 mg; I: 20 mg | i.v. | - |
| [40] Younger JW | 10 B | 0/10 | Mean: 55 ± 8 SD | NTx | 50 mg | p.o. | - |
| [41] Bruehl S | 39 C | 11/28 | Mean: 31 ± 8 SD | Nx | I: 8 mg | i.v. | - |
| [42] Bruehl S | 31 D | 13/18 | Mean: 34 ± 10 SD | Nx | I: 8 mg | i.v. | Morphine |
| Electrical: | |||||||
| [43] El-Sobky A | 5 | NR | NR | Nx | I: 0.4 mg; I: 0.8 mg | i.v. | - |
| [44] Buchsbaum MS | 21 | 10/11 | Mean: 20 | Nx | I: 2 mg | i.v. | - |
| [45] Bromm B | 15 | 15/0 | Range: 21–29 | Nx | 32 mg E | p.o. | Tilidine |
| Ischemia | |||||||
| [46] Grevert P | 12 | 6/6 | Median: 28 | Nx | B: 10 mg; B: 2 mg | i.v. | - |
| [47] Grevert P | 12 | 12/0 | Mean: 25 ± 3 SD | Nx | B: 10mg + I: 6 mg/h (8 hr); B: 2 mg + I: 1.2 mg/h (8 hr) | i.v. | - |
| [48] Posner J | 12 | NR | Range: 20–46 | Nx | I: 2 mg F | i.v. | Codeine p.o. |
| Mechanical: | |||||||
| [49] Schobel HP | 9 G | 9/0 | Mean: 25 ± 6 SD | Nx | I: 0.15 mg/kg | i.v. | - |
| [50] Cook DB | 12 | 12/0 | Mean: 24 ± 4 SD | NTx | 50 mg H | p.o. | Codeine p.o. |
| Thermal: | |||||||
| [51] Lautenbacher S | 11 I | 0/11 | Mean: 23 ± 3 SD | Nx | I: 5 mg | i.v. | - |
| [52] Lautenbacher S | 10 J | 12/8 | Mean: 36 ± 11 | Nx | I: 5 mg | i.v. | - |
| [53] Al’Absi M | 26 | 15/11 | Mean: 21 ± 9 | NTx | 50 mg | p.o. | |
| [54] Borras MC | 10 | 10/0 | Mean: 32 ± 7 | Nx | B: 4 mg | i.v. | - |
| [55] Kern D | 12 | 6/6 | Range: 21–38 | Nx | B: 0.1 mg/kg; I: 0.1 mg/kg/h (0.05 mg/kg) K | i.v. | Ketamine |
| [56] Kotlyar M | 19 | 9/10 | Mean: 26 ± 7 | NTx | 50 mg | p.o. | - |
| [57] Schoell ED | 16 L | 8/8 | Mean: 29 ± 5 | Nx | B: 0.15 mg/kg; I: 0.2 mg/kg/h | i.v. | - |
| [58] Pickering G | 10 M | 10/0 | Mean: 26 ± 2 SD | Nx | I: 8 mg N | i.v. | Paracetamol i.v. |
| Nociceptive Reflex Models | |||||||
| [59] Boreau F | 10 | 6/4 | Range: 22–33 | Nx | B: 0.8 mg | i.v. | - |
| [60] France CR | 158 | 85/73 | Mean: 19 ± 2 SD | NTx | B: 50 mg | p.o. | - |
| [61] France CR | 151 | 83/68 | Mean: 19 ± 2 SD | NTx | B: 50 mg | p.o. | - |
| Miscellaneous Models | |||||||
| [62] Eissenberg T | 12 | 8/4 | Mean: 22 ± 3 SD | NTx | B: 50 mg | p.o. | Oxycodone |
| [63] Robertson LJ | 24 | 9/15 | Median: 26; Range: 17–39 | Nx | B: 80 microg/0.2 ml (burn site) | s.c. | Fentanyl |
| Total all studies | 1,477 | ||||||
§ not interfering with the MOR-antagonist assessments (drugs without administration route stated are i.v.).
# 1mg: cold water challenge; 2mg: ischemic pain challenge.
A study includes fibromyalgia patients (n = 15, data not reported here).
B study includes fibromyalgia patients (n = 10, data not reported here).
C study included patients with chronic low back pain (n = 37; data not reported here) and 2 healthy subjects on antidepressant medication.
D study includes chronic low back pain patients (n = 45, data not reported here).
E study includes treatment arms of combinations of tilidine (100 mg) and naloxone (8–32 mg; data not reported here).
F study includes treatment arms with codeine (60 mg p.o.) and codeine/naloxone (2 mg i.v.; data not reported here).
G study includes subjects with borderline hypertension (n = 21, data not reported here).
H study includes treatment arm with codeine (60 mg p.o.; data not reported here).
I study includes patients with bulimia nervosa (n = 10) and anorexia nervosa (n = 10; data not reported here).
J study includes patients with major depression (n = 20; data not reported here).
K study includes placebo-controlled treatment arm with ketamine (0.4 mg/kg; data not reported here).
L the total number of subjects were 20 (4 were excluded).
M the total number of subjects were 12 (2 were excluded).
N study includes treatment arms with paracetamol (1g i.v.) and paracetamol/naloxone (8 mg i.v.; data not reported here).
SD standard deviation.
For explanation of abbreviations, please, refer to legend Table 3.