Neuropathic pain can arise as a result of direct trauma to nerves or indirectly as a secondary consequence of a diverse range of disease states including metabolic disorders (diabetes), cancer, chemotherapy, autoimmune disease (multiple sclerosis, AIDs), viral infection (postherpetic neuralgia), and stroke. Patients with neuropathic pain can present any number of positive symptoms as typified by spontaneous pain, pain evoked by normally innocuous sensory stimuli (allodynia), or exacerbated pain in response to noxious stimuli (hyperalgesia). Paradoxically, negative symptoms are also common and generally include loss of sensation around the area of injury. Preclinical studies have clearly demonstrated that altered functioning of voltage-activated Na+ and Ca2+ ion channels are key mediators of injury-induced hyperexcitability within pain processing pathways. These findings are mirrored in the clinical treatment of patients where antiepileptic drugs such as the Na+ channel blocker lamotrigine and gabapentin (which binds to the Ca2+ channel R2δ subunit) have proven to be variably effective in alleviating signs and symptoms of pain. Nevertheless, a significant number of patients receive inadequate treatment from these drugs and from other medications that include opiates and antidepressants. Therefore, novel mechanism of action drugs must be developed to help fulfill the unmet needs of patients. To this end, drugs capable of modulating voltage-activated Kv7 channels are particularly appealing, given that these channels play a key role in controlling the excitability status of neurons within the nervous system.