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potent in antagonizing morphine- than D-propoxyphene-induced antinoci- ception in the mouse hot-plate test. In morphine.tolerant mice showing 3-fold lower morphine sensitivity the antinociceptive efficacy of D-propoxy- phene was unchanged. The results indicate differences in receptor-effector mechanisms between D-propoxyphene and morphine. It is proposed that D-propoxyphene acts on several receptor populations due to lower selectiv- ity. The net antinociceptive effect would be the sum of interactions with different receptor populations. Due to its low sensitivity, D-propoxyphene would be less sensitive to site-specific antagonists in vivo provided that other sites also mediated the same biological response.

Increase of substance P in primary afferent nerves during chronic p a i n . - F. Lembeck, J. Donnerer and F.C. Colpaert, Neuropeptides, 1 (1981) 175--180

Substance P appears to be involved in the transmission of pain since it is present in small diameter sensory neurons, can be released from the spinal cord by sthnulation of AS/C fibers and excites neurons in the dorsal horn which are also activated by noxious stimuli. In this paper substance P con- tent was investigated in sensory nerves innervating the inflamed painful area in rats in which an adjuvant-induced polyarthritis caused a reproducible pathological condition associated with severe chronic pain. Substance P was measured with a sensitive and specific radioimmunoassay. In the arthritic groups the substance P content of the sciatic nerve showed a 174% increase over the control group. Smaller but not statistically significant increases were also found in the saphenous nerve, in the dorsal root ganglia and in the dorsal roots. Therefore, the substance P concentration in arthritic rats is increased only in the peripheral branch of sciatic nerve afferents. An increase in substance P synthesis, increased velocity or increased transport quanta in the axons, but also a diminished release are possible causes. However, since the experimental manipulation undoubtedly acts to stimulate afferent helves, it seems likely that the effects observed in this paper result from the increased peripheral release of substance P which can similarly be produced by electrical stimulation of pain fibers.

Dopaminergic involvement in the hyperalgesic effect of nomi f e ns ine . - J.P. Gonzalez, R.D.E. Sewell and P.S.J. Spencer, Life Sci., 28 (1981) 951--956

Tricyclic antidepressants are commonly used in chronic pain treatment. Conversely, the present paper demonstrates that nomifensine, which belongs to the methylphenidate group and clinically has been shown to be an effec- tive antidepressant comparable to imipramine and amitriptyline, produced a dose-related hyperalgesia in the tail immersion test using a 45°C stimulus. Nomifensine is a potent inhibitor of both noradrenaline and dopamine. Its analgesic activity was abolished by the dopamine antagonists haloperidol and pirnozide but remained unchanged by the relatively selective adrenergic antagonists phentolamine, phenoxybenzamine or propranolol. Thus it is postulated that there is a dopaminergic involvement in nomifensine hyperal- gesia to the exclusion of an adrenergic mechanism.