The American Academy of Pain Management estimates 50 million Americans suffer from chronic pain. A study conducted in 2000 surveyed millions of American patients; 83 million indicated that pain had affected their lives in various activities. Often pain goes untreated, or if it is treated it is done so poorly. In Canada and the United States, abuse of prescription pain-killers has risen dramatically since the 1990’s resulting in stricter guidelines for prescribing physicians; many doctors are reluctant to write out a script for a narcotic pain-killer to non-cancer patients, even if they clearly need it. A study conducted by Clinical Pharmacology and Therapeutics (2011) found that more and more adolescents are abusing narcotic analgesics for, not pain, but sexual facilitation — its no wonder doctors are hesitant to prescribe narcotics. Those of us who suffer from disabling, chronic medical conditions find it is getting harder and harder to receive adequate treatment for our pain. In many ways the media coverage is a good thing — it alerts doctors that they need to be careful who they prescribe certain medications too; however, the constant reports and articles about narcotic abuse in patients receiving treatment creates a false portrait of the greater population of pain-patients and establishes a schema doctors readily engage when they decide who to prescribe too.
Pain sensations usually arise in sensory neurons of the peripheral nervous system, which then relay information back to the Central nervous system. Pathological pain sensations (as in the case of chronic pain) can arise from changes in excitability of these peripheral sensory neurons. Voltage-gated sodium channels are key determinants regulating action potential generation and propagation; thus, changes in sodium channel function can have profound effects on neuronal excitability and pain signalling. At present, most of the clinically available sodium channel blockers used to treat pain are non-selective across sodium channel isoforms and can contribute to cardio-toxicity, motor impairments, and CNS side effects. Numerous strides have been made over the last decade in an effort to develop more selective and efficacious sodium channel blockers to treat pain. The current goal of most pharmaceutical companies investigating new ways of treating neuropathies is to develop more targeted sodium channel therapies.
A new study published in the British Journal of Pharmacology (2011) looks at the targeting of sodium channel blockers into nociceptors to produce long duration analgesia. The researchers concluded that targeting these charged sodium channel blockers into specific axons provides an opportunity to produce prolonged local analgesia. This approach is a little different. Instead of de-activating electrical or chemically gated sodium channels, researchers targeted charged lidocaine into nociceptive sensory neurons through the large-pore transient receptor potential cation channel to produce prolonged analgesia. This new method could represent a much more effective way of administering analgesics.
There are some cases where people cannot feel any pain at all; Congenital Insensitivity to Pain is one of them. We now know, through genetic testing, that CIP is caused by genes that result in the deactivation of the sodium channel Nav1.7. They have thus linked a loss of Nav1.7 function to insensitivity to pain. Conversely, persons who have an overactive Nav1.7 channel, as is the case in primary erethromelalgia, experience excruciating neuropathic pain. As a result of these findings, investigative studies into the potential role of Nav1.7 channel drugs could have in pain management have begun. Research conducted by Cayman Chemical is investigating the role of Nav1.7 sodium channel monoclonal antibodies in mice. Because Nav1.7 channels are not found in cardiac or neurons in the central nervous system, drugs which affect these receptors will have less side-effects than current medications. These researchers hope their results will allow them to develop drugs which will reduce the pain intensity in animals.
One of the most difficult forms of pain to treat is neuropathic pain, which is caused by primary lesion or dysfunction of the peripheral nervous system. Sodium channels are thought to play a central role in the pathophysiological hyperexcitability of this form of pain by initiating and propagating most signals. The current sodium channel programs for these types of pain-related disorders focus primarily around epilepsy; however, drugs used for the treatment of epilepsy often come with many unwanted side-effects (dizziness, drowsiness, fatigue, depression and sleeping disorders etc…). Washington state department for labour and industries issued some guidelines for physicians prescribing antiepileptic drugs (AED) for pain. They note that there is insufficient data to support the use of AEDs in cases of acute, low-back, somatic, and myofascial pain. They also indicate that, although neuropathies can be treated successfully with AEDs, this is not always the case; it depends exclusively upon which medication is chosen, and the person for which the medication is chosen for. They state that gabapentin has shown the highest efficacy and should be used as a first line treatment for conditions associated with known secondary neuropathies. Gabapentin’s effects can be seen within 4-6 weeks, at a maximum dose of 1800mg a day — titration to 2400mg a day can be done, but it shows no significant clinical difference; the absorption of gabapentin is not dose -proportional (that is, less of the medication is absorbed the more you take).
Researchers at Yale have begun collaborating with Pfizer to develop novel treatments for a rare pain disorder (Inherited Erythromelalgia). Inherited Erythromelalgia (IE), also known as ‘man-on-fire syndrome’, causes debilitating and life-long burning pain. As we’ve noted previously, sodium channels are basically molecular generators producing electrical impulses (action potentials). Mutations in these sodium channels cause them to be over-active. They hope that by blocking them, they will be able to effectively treat these patients — which up until now, have no currently known treatment options. This targeted study will fall under Icagen’s broader research into sodium channels to find treatments for various pain conditions. CEO of Icagen, Kay Wagoner stated in a press release “We are very pleased to report positive progress in our sodium channel pain collaboration with Pfizer in which compounds are now being advanced into first-in-man studies. As we have reported previously, the scientific partnership between Icagen and Pfizer has been successful in identifying novel, potent and selective blockers of the sodium channel Nav1.7, also referred to as SCN9A. Loss of function mutations of this channel have been genetically linked to the congenital inability to experience pain, and conversely gain of function mutations are implicated in the pain underlying primary Erythromelalgia and paroxysmal extreme pain disorder. Based upon these genetic linkages, Nav1.7 is believed to be among the most promising targets for new pain therapeutics.”
It seems as though pain is just one of those things that will be around forever. Although it does have an adaptive function, when it becomes pathological it loses all virtue. Chronic pain is a disabling condition that can leave people hopeless and broken. I often think my own suffering is the ‘worst in the world’. Although EDS can be pretty bad, it has treatment options. I cannot imagine having IE and experiencing burning pain without any beneficial treatment. It would be heavy-handed to conclude that the research currently being conducted will finally remove the hold pain has on many of our lives, but that doesn’t mean that it can’t be adequately treated to a level where we can function normally.