Anti-inflammatory Medication
Opioid Pain Medication


Non-steroidal anti-inflammatories, such as aspirin, tolmetin sodium, indomethacin and ibuprofen, inhibit the enzyme cyclooxygenase and therefore decrease prostaglandin synthesis. Prostaglandins are inflammatory mediators that are released during allergic and inflammatory processes. Phospholipase A2 enzyme, which is present in cell membranes, is stimulated or activated by tissue injury or microbial products. Activation of phospholipase A2 causes the release of arachidonic acid from the cell membrane phospholipid. From here there are two reaction pathways that are catalyzed by the enzymes cyclooxygenase and lipoxygenase. The cyclooxygenase enzyme pathway results in the formation of inflammatory mediator prostaglandins and thromboxane.

New generation Non-steroidal anti-inflammatories, such as Licofelone inhibit both enzymes cyclooxygenase and lipoxygenase therefore decreasing prostaglandin and leukotriene synthesis.

CORTICOSTEROID e.g. Solumedrol, Decadron, Triamcinolone

Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid’s intended action. Such actions can include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue and a general suppression in immune response. The degree of clinical effect is normally related to the dose administered. The anti-inflammatory corticosteroids inhibit the activation of phospholipase A2 by causing the synthesis of an inhibitory protein called lipocortin. It is lipocortin that inhibits the activity of phospholipases and therefore limits the production of potent mediators of inflammation such as prostaglandins and leukotriene.

Corticosteroids are also effective for some types of neuropathic pain and complex regional pain syndromes. One study examined the effects of systemic methylprednisolone on acute pain and pain hypersensitivity in normal and neuropathic rats.. In this study, when systemic methylprednisolone was started immediately after sciatic and saphenous nerve injury, there was a dose-dependent reduction in autotomy behavior. Substance P is an inflammatory mediator of neuropathic pain and edema. Single dose methylprednisolone (12 mg/kg) slightly reduced the substance P mediated inflammation induced with electrical stimulation of the saphenous nerve. Chronic methylprednisolone (3.4 mg/kg per day for 28 days) severely reduced the neurogenic inflammation induced with saphenous nerve stimulation.. Rats with sciatic nerve injury developed hind paw edema between 7 and 14 days after surgery, and this neuropathic edema did not develop in rats chronically treated with methylprednisolone (3.4 mg/kg per day). The study results demonstrate that corticosteroids did not affect pain thresholds in normal or neuropathic rats. However, chronic steroid treatment did prevent the development of autotomy and neuropathic edema, and completely blocked neurogenic extravasation, findings consistent with the hypothesis that primary afferent substance P release mediates autotomy pain behavior and neuropathic edema [89] [40].

OPIOID PAIN MEDICATION e.g. Methadone, Morphine

Opioid medication such as Methadone, Oxycodone, Morphine, Demerol and Vicodin produce pain relief by binding and activating specialized opioid receptors at the site of tissue injury and in an area of the spinal cord called the substantia gelatinosa. Once activated, the opioid receptors inhibit the release of inflammatory mediators such as bradykinin at site of tissue injury and Substance P from pain transmitting C nerve fibers. The pain receptors that were previously excited are now suppressed. There is also suppression of the signal traffic in the specialized nerves e.g. C fibers and A-delta fibers that carry pain impulses to the spinal cord and brain. Morphine and other opioids also alter emotional processing of painful input by acting on opioid receptors in the limbic and cortical area of the brain. In addition, new research now shows that morphine and other opioids have additional anti-inflammatory effects. These effects include:

1. Inhibition of Interleukin-1 beta converting enzyme (ICE), a proteolytic enzyme that converts the inactive precursor of interleukin-1 beta (Interleukin-1 beta) to its mature active form [90] [41]

2. Inhibit inflammatory cytokine mediators interferon-alpha IFN (IFN-alpha) and interferon-beta (IFN-beta) production by lymphocytes and fibroblast cells [91] [42]

3. Inhibits tumor necrosis factor-alpha (TNF-alpha) production by activated macrophages [92] [43]

4. Induces the suicidal cell death (apoptosis) of immune cell lymphocytes.

5. Increases the release of anti-inflammatory cytokines such as transforming growth factor-beta1 (TGF-beta1) and Interleuken-10 [93] [44].

Morphine and other opioids are also effective anti-migraine agents. In electrophysiological studies morphine significantly attenuated brainstem neuronal activity in response to electrical stimulation of the dura by 65%. Morphine also inhibited the trigeminal nucleus caudalis (TNC) neuronal sensitization following calcitonin gene-related peptide (CGRP)-evoked dilation. Studies have demonstrated that opioids block the nociceptive neurotransmission within the trigeminal nucleus caudalis and in addition inhibit neurogenic dural vasodilation via an action on mu-opioid receptors located on trigeminal sensory fibres innervating dural blood vessels [94] . These peripheral and central actions could account for the anti-migraine actions of opioids.