The involvement of tachykinin neuropeptides, such as substance P and the neurokinins, in pain transmission is supported by a wealth of evidence. At present, the therapeutic potential of manipulating tachykinin-mediated effects is being investigated and has been assisted by the discovery of several non-peptide, metabolically stable compounds that are antagonists at neurokinin (NK) receptors. Since multiple neurotransmitters or neuromodulators are involved in nociception in primary afferents, drugs that are antagonists at both tachykinin NK1and NK2receptors could be clinically more useful than receptor-selective drugs in the treatment of pain syndromes. NK1receptor antagonists that are also opioid receptor agonists or the combination of neurokinin receptor antagonists with opioids may also be promising approaches to treating pain.