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Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats.
J Opioid Manag. 2011 Sep-Oct; 7(5):377-89.JO

Abstract

BACKGROUND

In addition to producing analgesia, opioids can increase sensitivity to pain (opioid-induced hyperalgesia [OIH]) in humans and rodents. Tolerance/OIH is likely mediated by similar mechanisms that lead to development of hyperalgesia after nerve injury (neuropathic pain). OIH may be a reason for loss of opioid efficacy and/or a worsening of pain. Ultra-low-dose (ULD) opioid evokes hyperalgesia independently of analgesia. Tolerance to ULD-OIH develops with repeated dosing in rats.

OBJECTIVE

The effects of ULD opioids were characterized in two distinct situations where hyperalgesia is expected to occur: following acute opioid treatment and after nerve injury.

DESIGN

First, ULD morphine was repeatedly administered (2x day for 5 days) by intrathecal (i.t., 0.01 microg) or intraperitoneal (i.p., 20 microg/kg) routes in rats. Second, morphine (0.01 microg i.t.; 20 microg/kg i.p.) was administered (2x day for 5 days) prior to acute morphine (30 microg i.t.; 10 mg/kg i.p). Third, ULD morphine (20 microg/kg/2x day, i.p.) was given either immediately after nerve injury (days 1-28) or when hyperalgesia was manifested (days 7-14). The tail-flick and paw-pressure tests were used in noninjured and nerve-injured rats, respectively.

RESULTS

Tolerance was developed to OIH with repeated ULD morphine by the i.p. route but not the i.t. route. Prior exposure to ULD morphine (i.p.) caused prolongation of morphine analgesia in intact rats and inhibition of the development (but not reversal) of hyperalgesia in nerve-injured rats. Abolishment of OIH (pain desensitization) may diminish activation of pain facilitatory systems due to nerve injury and opioid treatment.

CONCLUSIONS

Although the translational aspect of this preclinical study has limitations, the present data may suggest a new strategy for the pre-emptive use of ULD opioids to prevent the development of neuropathic pain with certain procedures or disease states.

Authors+Show Affiliations

Department of Anesthesiology, College of Medicine, University of Kentucky, Lexington, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22165037

Citation

Wala, Elzbieta P., et al. "Effect of Prior Treatment With Ultra-low-dose Morphine On Opioid- and Nerve Injury-induced Hyperalgesia in Rats." Journal of Opioid Management, vol. 7, no. 5, 2011, pp. 377-89.
Wala EP, Sloan PA, Holtman JR. Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats. J Opioid Manag. 2011;7(5):377-89.
Wala, E. P., Sloan, P. A., & Holtman, J. R. (2011). Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats. Journal of Opioid Management, 7(5), 377-89.
Wala EP, Sloan PA, Holtman JR. Effect of Prior Treatment With Ultra-low-dose Morphine On Opioid- and Nerve Injury-induced Hyperalgesia in Rats. J Opioid Manag. 2011 Sep-Oct;7(5):377-89. PubMed PMID: 22165037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of prior treatment with ultra-low-dose morphine on opioid- and nerve injury-induced hyperalgesia in rats. AU - Wala,Elzbieta P, AU - Sloan,Paul A, AU - Holtman,Joseph R,Jr PY - 2011/12/15/entrez PY - 2011/12/15/pubmed PY - 2012/1/4/medline SP - 377 EP - 89 JF - Journal of opioid management JO - J Opioid Manag VL - 7 IS - 5 N2 - BACKGROUND: In addition to producing analgesia, opioids can increase sensitivity to pain (opioid-induced hyperalgesia [OIH]) in humans and rodents. Tolerance/OIH is likely mediated by similar mechanisms that lead to development of hyperalgesia after nerve injury (neuropathic pain). OIH may be a reason for loss of opioid efficacy and/or a worsening of pain. Ultra-low-dose (ULD) opioid evokes hyperalgesia independently of analgesia. Tolerance to ULD-OIH develops with repeated dosing in rats. OBJECTIVE: The effects of ULD opioids were characterized in two distinct situations where hyperalgesia is expected to occur: following acute opioid treatment and after nerve injury. DESIGN: First, ULD morphine was repeatedly administered (2x day for 5 days) by intrathecal (i.t., 0.01 microg) or intraperitoneal (i.p., 20 microg/kg) routes in rats. Second, morphine (0.01 microg i.t.; 20 microg/kg i.p.) was administered (2x day for 5 days) prior to acute morphine (30 microg i.t.; 10 mg/kg i.p). Third, ULD morphine (20 microg/kg/2x day, i.p.) was given either immediately after nerve injury (days 1-28) or when hyperalgesia was manifested (days 7-14). The tail-flick and paw-pressure tests were used in noninjured and nerve-injured rats, respectively. RESULTS: Tolerance was developed to OIH with repeated ULD morphine by the i.p. route but not the i.t. route. Prior exposure to ULD morphine (i.p.) caused prolongation of morphine analgesia in intact rats and inhibition of the development (but not reversal) of hyperalgesia in nerve-injured rats. Abolishment of OIH (pain desensitization) may diminish activation of pain facilitatory systems due to nerve injury and opioid treatment. CONCLUSIONS: Although the translational aspect of this preclinical study has limitations, the present data may suggest a new strategy for the pre-emptive use of ULD opioids to prevent the development of neuropathic pain with certain procedures or disease states. SN - 1551-7489 UR - https://www.unboundmedicine.com/medline/citation/22165037/Effect_of_prior_treatment_with_ultra_low_dose_morphine_on_opioid__and_nerve_injury_induced_hyperalgesia_in_rats_ DB - PRIME DP - Unbound Medicine ER -