====== Pregabalin for Neuropathic Pain ======

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Pregabalin is often prescribed for [[neuropathic pain]] conditions, such as [[diabetic neuropathy]], [[postherpetic neuralgia]], and [[peripheral neuropathy]].
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Neuropathic pain can be a component of [[radiculopathy]]. When the [[nerve root]]s are compressed or irritated in radiculopathy, it can lead to abnormal signaling and sensations, contributing to neuropathic pain.

Radiculopathy is a specific anatomical condition involving the spinal nerves, whereas neuropathic pain is a broader term describing pain resulting from nerve damage or dysfunction.

In summary, while radiculopathy involves compression or irritation of [[spinal nerve root]]s, [[neuropathic pain]] is a broader term referring to pain arising from damage or [[dysfunction]] of the nervous system. [[Radiculopathy]] can be a specific cause of neuropathic pain when it affects the nerves exiting the spinal cord.
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The probable [[mechanism of action]] is to reduce the release of several [[excitatory neurotransmitter]]s by inhibiting calcium influx via the calcium channels
((Rose MA, Kam PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia 2002; 57:451-62.))
((Arikkath J, Campbell KP. Auxillary subunits: essential components of the voltage-gated calcium channel complex. Curr 
Opin Neurobiol 2003; 13:298-307.))
((Gee NS, Brown JP, Dissanayake VU, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the 
alpha2delta subunit of a calcium channel. J Biol Chem 1996; 271:5768-76.))
((Taylor CP. The biology and pharmacology of calcium channel alpha-2-delta proteins. CNS Drug Rev 2004; 10:183-8)).

Pregabalin is pharmacologically superior to gabapentin due to its higher bioavailability (90% vs. 33%–66%), more rapid absorption (peak plasma level: 1 hr vs. 3–4 hrs) and linear increase in plasma concentration when its dose is increased. Lower doses of pregabalin than that of gabapentin (2–4 fold lower doses) have a similar analgesic effect on neuropathic pain, which makes pregabalin more advantageous in terms of the side effects from dosage
((Field MJ, Oles RJ, Lewis AS, et al. Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective
antihyperalgesic agents. Br J Pharmacol 1997; 121:1513-22.
((Partridge BJ, Chaplan SR, Sakamoto E, Yaksh TL. Characterization of the effects of gabapentin and 3-isobutyl-gaminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology 1998; 88:196-205.))
((Jun JH, Yaksh TL. The effect of intrathecal gabapentin and 3-isobutyl g-aminobutyric acid on the hyperalgesia obseved
after thermal injury in the rat. Anesth Analg 1998; 86:348-54.))
((Field MJ, Holloman EF, McCleary S, Hughes J, Singh L. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat
model of postoperative pain. J Pharmacol ExpTher 1997; 282:1242-6.)).

Perioperative PG administration reduces early postsurgical pain at rest and particularly during movement after major spine surgery with less opioid consumption, and it seems to influence the improvement of overall QoL 3 months after surgery
((Gianesello L, Pavoni V, Barboni E, Galeotti I, Nella A. Perioperative pregabalin for postoperative pain control and quality of life after major spinal surgery. J Neurosurg Anesthesiol. 2012 Apr;24(2):121-6. doi: 10.1097/ANA.0b013e31823a885b. PubMed PMID: 22045156.)).

Preoperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy followed by [[gabapentin]] and then placebo.Level of Evidence: 2
((Khurana G, Jindal P, Sharma J, Bansal K. Post Operative Pain and Long Term Functional Outcome Following Administration of Gabapentin & Pregabalin in Patients Undergoing Spinal Surgery. Spine (Phila Pa 1976). 2013 Dec 30. [Epub
ahead of print] PubMed PMID: 24384657.)).

Both pregabalin 300 mg day-1 and gabapentin 1,200 mg day-1 have more analgesic, anxiolytic and opioid-sparing effects, higher patient satisfaction and are more effective for preventing postoperative shivering than the placebo following lumbar laminectomy and discectomy. Findings revealed that pregabalin 300 mg day-1 had equivalent analgesic, adverse and opioid-sparing effects and patient satisfaction as gabapentin 1,200 mg day-1
((Ozgencil E, Yalcin S, Tuna H, Yorukoglu D, Kecik Y. Perioperative administration of gabapentin 1,200 mg day-1 and pregabalin 300 mg day-1 for pain following lumbar laminectomy and discectomy: a randomised, double-blinded,
placebo-controlled study. Singapore Med J. 2011 Dec;52(12):883-9. PubMed PMID: 22159931.)).

Combined administration of pregabalin and dexamethasone conferred analgesic benefits superior to those of pregabalin alone. This regimen also helped facilitate return to normal daily activity after surgery
((Choi YS, Shim JK, Song JW, Kim JC, Yoo YC, Kwak YL. Combination of pregabalin and dexamethasone for postoperative pain and functional outcome in patients undergoing lumbar spinal surgery: a randomized placebo-controlled trial. Clin J
Pain. 2013 Jan;29(1):9-14. doi: 10.1097/AJP.0b013e318246d1a9. PubMed PMID: 22751028.)).

====Dose====
Perioperative administration of pregabalin 150 mg before and 12 hours after surgery, but not 75 mg, significantly reduced opioid consumption and the use of additional pain rescue for 48 hours after surgery without significant side effects in patients undergoing spinal fusion surgery
((Kim JC, Choi YS, Kim KN, Shim JK, Lee JY, Kwak YL. Effective dose of peri-operative oral pregabalin as an adjunct to multimodal analgesic regimen in lumbar spinal fusion surgery. Spine (Phila Pa 1976). 2011 Mar 15;36(6):428-33. doi: 10.1097/BRS.0b013e3181d26708. PubMed PMID: 21372654.)).

===== Evidence =====

There is high-[[quality]] [[evidence]] that [[Nonsteroidal anti-inflammatory drug]]s reduces pain up to 24 hours postoperatively. The evidence for reductions in pain with [[dexmedetomidine]], [[pregabalin]] or [[gabapentin]], [[scalp block]]s, and [[scalp]] [[infiltration]] is less certain and of very low to moderate quality. There is low-quality evidence that scalp blocks and dexmedetomidine may reduce additional analgesics requirements. There is low-quality evidence that [[gabapentin]] or [[pregabalin]] may decrease nausea and vomiting, with the caveat that the total number of events for this comparison was low
((Galvin IM, Levy R, Day AG, Gilron I. Pharmacological interventions for the
prevention of acute postoperative pain in adults following brain surgery.
Cochrane Database Syst Rev. 2019 Nov 21;2019(11). doi:
10.1002/14651858.CD011931.pub2. Review. PubMed PMID: 31747720.
)).

===== Pregabalin for chronic low back pain treatment =====
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[[Gabapentin]] and [[pregabalin]] are often used in the treatment of patients without associated [[radiculopathy]] or [[neuropathy]]. Therefore, determining their efficacy and safety is of enormous value.

Tatit et al. performed a search on the [[CENTRAL]], [[MEDLINE]], [[EMBASE]], [[LILACS]], and [[Web of Science]] databases for [[clinical trial]]s, cohorts, and [[case-control]] studies that evaluated patients with CLBP without radiculopathy or neuropathy for at least eight weeks. The data were extracted and inserted into a previously prepared Microsoft Excel spreadsheet; the outcomes were evaluated using the Cochrane RoB 2 tool, and the quality of evidence, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Of the 2,230 articles identified, only 5 were included, totaling 242 participants. In them, pregabalin was slightly less efficacious than amitriptyline, the combination of tramadol/acetaminophen, and celecoxib, and pregabalin added to celecoxib showed no benefit when compared to celecoxib alone (very low evidence for all). On the other hand, although one study with gabapentin did not support its use in a general sample of patients with low back pain, another found a reduction in the pain scale and improved mobility (moderate evidence). No serious adverse events were observed in any of the studies.

[[Quality]] information to support the use of pregabalin or gabapentin in the treatment of CLBP without radiculopathy or neuropathy is lacking, although results may suggest gabapentin as a viable option. More data is needed to fill this current gap in knowledge
((Tatit RT, Poetscher AW, Oliveira CAC. Pregabalin and gabapentin for chronic low back pain without radiculopathy: a systematic review. Arq Neuropsiquiatr. 2023 Jun;81(6):564-576. doi: 10.1055/s-0043-1764414. Epub 2023 Jun 28. PMID: 37379868; PMCID: PMC10306996.)).

===== Pregabalin for radiculopathy  =====

[[Pregabalin for radiculopathy]].


====Case series====
Of 105 patients who entered the run-in period, 47 patients (44.8%) were female and 58 (55.2%) were male. The Patients radicular pain mean score based on Numerical scale system (NRS) estimated before surgery was 7.22±1.95 in pregabalin14, 7.71±1.84 in pregabalin1 and 7.45±1.9 in control group. There were no statically significant differences between three groups (P-Value>0.05). The Patient [[back pain]] mean score based on NRS was 5.2±2.87 in pregabalin14, 5.11±3.23 in pregabalin1 and 6.4±3.06 in control group. This means that there were no significant differences in the overall score among those three groups (P-Value>0.05). In comparison to their preoperative pain, the average radicular pain in each group of patients improved significantly 4, 8, 12 and 24h after the operation (P-Value<0.001), but there were no significant differences in radicular pain improvements comparing three groups.

The results of this study indicate that 1day and 2 weeks post-operative 300mg pregabalin administration may not improve acute pain, morphine consumption and quality of life of patients after surgery. It seems that the diseases cause chronic pain that requires long-term treatment with higher doses
((Zarei M, Najafi A, Mansouri P, Sadeghi-Yazdankhah S, Saberi H, Moradi M,
Farzan M. Management of postoperative pain after Lumbar surgery-pregabalin for
one day and 14 days-a randomized, triple-blinded, placebo-controlled study. Clin 
Neurol Neurosurg. 2016 Oct 17;151:37-42. doi: 10.1016/j.clineuro.2016.10.007.
PubMed PMID: 27764706.
)).
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[[Supratrochlear neuralgia]]-  [[Supraorbital neuralgia]] 
[[Gabapentin]] (800–2400 mg/d) or [[pregabalin]] (150 mg/d) is helpful for some
((Caminero AB, Pareja JA. Supraorbital neuralgia: a clinical study. Cephalalgia. 2001; 21:216–223)).

===== Pregabalin for Diabetic neuropathy =====

[[Pregabalin for Diabetic neuropathy]]