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Imagine having instant Electro House Revolution Vol.. The LinnDrum uses samples of acoustic drum sounds. Codeine is the most widely consumed opioid analgesic worldwide. It relies upon partial metabolism to morphine to elicit analgesic effects. Paradoxically, the pain-reliever morphine has previously been linked to states of increased pain sensitivity; such as medication overuse headache and opioid-induced hyperalgesia and allodynia.

Despite the clinical impact of medication overuse headache the pathophysiology behind this disorder remains unclear and mechanism-based treatments are lacking. Although most acute headache treatments are alleged to cause medication overuse headache, within this thesis we conclude from the literature opioids are the drug class most strongly associated with worsening headache. In opioid-induced hyperalgesia and allodynia sensitivity to normally noxious, and non-noxious stimuli respectively, are enhanced due to opioid exposure.

Chronic morphine may exacerbate pain in the long-term by non-specifically activating toll-like receptor-4 TLR4 on glial cells, resulting in a pro-inflammatory state that manifests clinically as increased pain. Here we hypothesise medication overuse headache is a specific form of opioid-induced hyperalgesia, which derives from a cumulative interaction between central sensitisation and glial priming, due to repeated activation of nociceptive pathways by recurrent headaches, and pain facilitation due to glial activation and subsequent neuroinflammation.

The first part of this thesis examines the efficacy of a glial-attenuating treatment, ibudilast, in the clinical management of medication overuse headache induced by opioid use in a double-blind, randomised, placebo-controlled parallel group study. Patients received ibudilast 40 mg twice daily or placebo for 8 weeks and recorded headache and analgesic intake using a headache diary for 4-weeks prior to randomisation and throughout the treatment phase.

Prior to this PhD project the relationship between codeine and increased pain sensitivity had not been investigated. Evidence that codeine can induce hyperalgesia would sit in line with our glial hypothesis for opioid overuse headache.

Thus, the second part of this PhD includes a series of preclinical experiments to 1. Our preclinical studies demonstrate that despite providing lesser acute analgesia, equimolar codeine and morphine induced similar hot plate hyperalgesia, suggesting codeine does not rely upon conversion to morphine to increase pain sensitivity, emphasising the non-opioid receptor-dependent nature of this phenomenon.

Glial attenuation with ibudilast reversed codeine-induced allodynia and thus could be investigated as potential treatment for conditions involving codeine-induced pain enhancement. Skip to content. Author : Brigid M.

Codeine Book Review:. Studies on Codeine Addiction. Studies on Codeine Addiction Book Review:. Acetaminophen codeine. Acetaminophen codeine Book Review:. Codeine and Acetaminophen for Pain Relief. Author : F. Author : Jaymin C. Codeine Phosphate.