Methods for treating acute and subchronic pain
Methods of potentiating opioid-induced analgesia in a subject by administration of a phosphodiesterase (PDE) inhibitor or glial attenuator are described. In particular, the present invention is directed to methods of treating or preventing acute or subchronic pain by administration of a PDE inhibitor or glial attenuator, such as ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine), in combination with an opioid.
1 . A method for enhancing the analgesic efficacy of an opioid in a subject, comprising administering to the subject an effective amount of a phosphodiesterase (PDE) inhibitor or glial attenuator that potentiates opioid-induced analgesia in the subject.
2 . The method of claim 1 , wherein the PDE inhibitor is a PDE 3, PDE 4, PDE 10 and/or PDE 11 inhibitor.
3 . The method of claim 2 , wherein the PDE inhibitor is a PDE 3 and/or PDE 4 inhibitor.
4 . The method of claim 1 , wherein the PDE inhibitor or glial attenuator is administered prior to the opioid.
5 . The method of claim 1 , wherein the PDE inhibitor or glial attenuator is administered concurrently with the opioid.
6 . The method of claim 1 , wherein the PDE inhibitor or glial attenuator is ibudilast.
7 . The method of claim 1 , wherein the opioid is morphine.
8 . The method of claim 1 , wherein the opioid is oxycodone.
9 . The method of claim 1 , wherein the PDE inhibitor is selected from the group consisting of Rolipram, Arofylline, Doxofylline, Cipamfylline, Roflumilast, Tetomilast, Atizoram, CC-1088, Tofimilast, Tolafentrine, Pentoxyfylline, Dipyridamole, Cilostazol, Theophylline, Cilomilast, AWD-12-28, Propentofylline.
10 . The method of claim 1 , wherein the glial attenuator is selected from the group consisting of Minocycline, Fluorocitrate, MW01-5-188WH, Propentofylline, Pentoxyfylline, Rolipram, IL-10, an IL-1 receptor antagonist, a TNF-receptor antagonist such as a sTNFR, MAP-kinase inhibitor, Yohimbine, a glial cell chloride antagonist, a caspase inhibitor, an MMP inhibitor, a cannabinoid receptor agonist, arundic acid, a statin, and thalidomide and related analogs.
11 . The method of claim 1 , wherein a reduced dose of opioid is administered to said subject relative to the dose of opioid required for an analgesic effect without the PDE inhibitor or glial attenuator.
12 . A method for treating acute or subchronic pain comprising administering to a subject in need thereof a therapeutically effective amount of ibudilast and an opioid.
13 . The method of claim 12 , wherein the ibudilast is administered to the subject prior to the opioid.
14 . The method of claim 12 , wherein the ibudilast is administered to the subject concurrently with the opioid.
15 . The method of claim 12 , wherein the ibudilast and opioid are in the same composition.
16 . The method of claim 12 , wherein the ibudilast and opioid are in separate compositions.
17 . The method of claim 12 , wherein the opioid is morphine.
18 . The method of claim 12 , wherein the opioid is oxycodone.
19 . The method of claim 12 , wherein the subject is human.
20 . The method of claim 12 , wherein the ibudilast is administered systemically.
21 . The method of claim 20 , wherein the ibudilast is administered intravenously, subcutaneously, intraperitoneally, orally, intranasally, or sublingually.
22 . The method of claim 21 , wherein the ibudilast is administered orally.
23 . The method of claim 21 , wherein the ibudilast is administered intraperitoneally.
24 . The method of claim 12 , wherein the ibudilast is administered centrally.
25 . The method of claim 24 , wherein the ibudilast is administered intrathecally.
26 . The method of claim 12 , wherein the opioid is administered subcutaneously.
27 . The method of claim 12 , wherein multiple therapeutically effective doses of the ibudilast and the opioid are administered to the subject.
28 . The method of claim 12 , wherein the acute or subchronic pain is post-operative pain, post-dental procedure pain, injury-related pain, or disease-related pain.
29 . The method of claim 12 , further comprising administering one or more other agents selected from the group consisting of analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines and antidepressants.