Treatments in testing

All of the classical analgesics work by attenuating steps within the chemical signalling pathways that evoke pain. Although effective, these analgesics often have unwanted side-effects since they act early on in the chemical pathway and thus affect numerous downstream processes. It follows then, that newer drugs in development will work within the same pathways, but perhaps be designed as more selective, thus reducing unwanted side-effects. Drugs currently under investigation include:

1. Blockers of ion channels specific to nociceptive nerves

 A recent study by Cox et al (2006) found that the voltage-gated Na channel Nav1.7 was implicated in the sensation of pain. They deduced this since this was the dysfunctional channel in patients suffering congenital insensitivity to pain. So it follows that a pharmacological agent that selectively blocks the action of this channel, could reduce pain.

2. Enkephalinase inhibitors (eg. thiorphan)

 In response to tissue damage, the body often produces its own morphine-like painkillers known as endorphins, to help us deal with intense pain sensations. These are broken down by encephalinase, and so it's only logical that inhibitors of encephalinase could enhance the body's natural mechanisms of pain reduction.

3. Antagonists of mGluR5

 Trials are currently underway for drugs that block the metabotrophic glutamate receptor 5, a transmitter receptor found on dorsal horn neurones. Blocking this receptor would prevent synaptic transmission in spinal pain neurones and thus prevent pain.

4. Neuropeptides such as calcitonin and somatostatin

 Calcitonin and somatostatin are hormones endogenous to the body. Calcitonin acts to reduce blood Ca, while somatostatin regulates GPCRs associated with neurotransmission. Injections of either of these hormones appears to alleviate pain. It is possible that this works by reducing Ca present in muscle etc, thus preventing cramping.

5. Agonists at specific nACh receptors

 While some labs are focused on receptor antagonists, some studies have found that agonists at certain nicotinic Acetylcholine receptors can induce a state of analgesia. The reasons for this are unknown, though it seems logical that the ACh works to activate neurons that inhibit pain neurons.

6. Cannabinoid receptor agonists

 Tetrahydrocannabinol (THC) has been shown to reduce neurotransmission in dorsal horn transmission neurones. THC is a derivative of cannabis, and so is a controversial agent.

7. Specific prostaglandin inhibitors

 As mentioned elsewhere, pain neurones are sensitised by prostaglandins upon inflammation of a tissue. Currently NSAIDs work to inhibit prostaglandin production alltogether by inhibiting the enzyme cyclo-oxygenase. This however has adverse side effects, since different prostaglandins have different physiological roles. A drug designed to SPECIFICALLY inhibit just PGI2 or PGE2 would reduce the sensation of pain, while leaving other physiological processes unaffected.