Table 2.
Summary of 50% antinociceptive values and (95% confidence limits).
| Test | |||||
|---|---|---|---|---|---|
| Acute/heat, μg (95% CL) | CCI/heat, μg (95% CL) | CCI/tactile, μg (95% CL) | Formalin, μg (95% CL) | ||
| Drug | Phase 1 | Phase 2 | |||
| EM-1 | 0 | >30 (16.4–130) | 13.5 (6.2–29) | 12.1 (3.8–38.7) | 40 (14.6–107) |
| EM-1 + SHG | >30 (12.2–122.3)† | >30 (30–200) | 13.9 (7.8–25) | 1.5 (0.7–3)† | 11 (5–22)† |
| EM-2 | 0 | 0 | 0 | 2.5 (1.2–5.1) | 0 |
| EM-2 + SHG | 0 | 0 | >30 (21–102)‡ | 4 (1.6–10.3) | 0 |
| Morphine | 5.4 (3.6–7.9) | 8 (3.4–18.5) | 0.6 (0.3–1.1) | 1 (0.4–2.3) | 1.5 (0.8–2.8) |
| Morphine + SHG | 2.6 (1.6–4.1)* | 3.3 (1.4–7.8) | 0.2 (0.1–0.4)* | 0.1 (0.04–0.5)* | 0.5 (0.2–1.1)* |
| Morphine + ketamine | 0.5 (0.4–0.7)* | 0.9 (0.6–1.3)* | 0.3 (0.2–0.6) | 0.1 (0.05–0.2)* | 0.002 (0.0005–0.008)* |
| SHG | 0 | 0 | 0 | 0 | 0 |
| Ketamine | 0 | 0 | 0 | 0 | 0 |
CL, confidence limits; CCI, chronic constriction injury; EM-1, endomorphin-1; EM-2, endomorphin-2; SHG, [Ser1]histogranin.
Fifty percent antinociceptive values, in μg, were calculated from the linear portion of the log dose–response curves (see Materials and Methods section). Values for acute/heat, CCI/heat, CCI/tactile were obtained at 30 min post injection. In the formalin test, Phase 1 data were obtained immediately following formalin injection (0–1 min) and Phase 2 data were obtained 15–61 min following formalin injection. The doses of SHG tested were 0.3 and 1 μg and for ketamine was 10 μg (see Table 1).
P < 0.05 versus EM-1 alone;
P < 0.05 versus EM-2 alone;
P < 0.05 versus morphine alone.