Two patients get the same injection into the same structure by the same physician. One is markedly better at six weeks. The other is not, and nothing about the procedure explains the difference.
The variable that most often separates them is not the joint. It is the body the joint is sitting in — and the same variable quietly determines how much pain medication a person ends up needing.
Fat tissue is an endocrine organ, not padding
Visceral adipose tissue secretes interleukin-6, tumor necrosis factor alpha and other cytokines directly into portal circulation. Those mediators do not stay local. They sensitize peripheral nociceptors and drive central sensitization in the dorsal horn, which lowers the threshold at which the nervous system reports pain at all.
The practical consequence is that a person carrying a high inflammatory load arrives with the volume already turned up, before any structural injury is considered. The scan may show the same disc as the next person. The experience is not the same, and neither is the dose it takes to make it tolerable.
Insulin resistance compounds it
Hyperglycemia impairs microvascular perfusion of peripheral nerve, and glycemic variability tracks with neuropathic pain intensity independently of average control. A patient whose glucose swings widely can have worse nerve pain than their A1c predicts — which is one reason a number that looks acceptable on paper does not settle the question.
Taken together, the terrain determines both how much pain a given structure generates and how well a repair placed into it will take. It is why the metabolic work here runs alongside a procedure rather than after it.
The medication runs the other way too
The relationship is not one-directional, and this is the part that is usually left out of the metabolic conversation.
Long-term opioid therapy suppresses the hypothalamic-pituitary-gonadal axis. The resulting hypogonadism is well described in the literature under the name opioid-induced androgen deficiency, and its documented consequences include reduced libido, fatigue, depression, loss of muscle mass, and reduced bone density. Reviews of opioid-related endocrinopathy note the same axis effects and add impaired fertility and osteoporosis.
Read that list next to the metabolic picture above and the overlap is obvious. Lost muscle mass and fatigue reduce activity; reduced activity worsens insulin sensitivity and raises inflammatory load; a higher inflammatory load lowers the pain threshold; a lower pain threshold raises the dose. It is a loop, and in a patient already carrying metabolic disease it closes quickly.
Which is why the dose is a terrain question
Sustained opioid exposure can also produce opioid-induced hyperalgesia — a recalibration of the pain system toward sensitivity, attributed to the central glutamatergic system and NMDA receptor activation, spinal dynorphin and descending facilitation. Where it is operating, more drug feeds the problem, and one review describes further prescribing as largely futile.
The corollary is the useful one. Reviews of tolerance and hyperalgesia note that interventional techniques reducing the pain input can allow the dose to fall and, in doing so, revert the mechanisms that drove it up. Treat the generator, change the terrain it sits in, and the requirement falls as a consequence rather than as a target.
Dr. Padda published his interventional practice’s own figures on that in August 2026: an average arrival dose above 90 morphine milligram equivalents a day after more than two and a half years in pain, 21% of patients completely off opioid pain medication within 90 days of active treatment and 34% within one year, and most of the remainder held below 30 MME a day. Those are practice-reported figures from a single population, not trial outcomes, and individual results vary. Reported by AP News; full release.
What this changes about a plan
It moves two things that are usually treated as separate problems onto the same page. If someone is carrying a high metabolic and inflammatory load and a long-standing opioid requirement, addressing either one alone tends to disappoint — the procedure underperforms in an inflamed body, and the dose will not come down while the terrain keeps regenerating the signal.
It also sets a realistic pace. Inflammatory load and insulin sensitivity move over months, not weeks, and the endocrine consequences of long-term opioid exposure do not reverse on the day the dose changes. A plan that assumes otherwise is setting up its own failure.
References
- Gudin JA, Laitman A, Nalamachu S. Opioid related endocrinopathy. Pain Medicine. 2015;16(Suppl 1):S9–S15. PMID 26461076 · DOI 10.1111/pme.12926.
- O’Rourke TK, Wosnitzer MS. Opioid-induced androgen deficiency (OPIAD): diagnosis, management, and literature review. Current Urology Reports. 2016;17(10):76. PMID 27586511 · DOI 10.1007/s11934-016-0634-y.
- Mercadante S, Arcuri E, Santoni A. Opioid-induced tolerance and hyperalgesia. CNS Drugs. 2019;33(10):943–955. PMID 31578704 · DOI 10.1007/s40263-019-00660-0.
- Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia — when is enough too much? A review of opioid-induced tolerance and hyperalgesia. The Lancet. 2019;393(10180):1558–1568. PMID 30983591 · DOI 10.1016/S0140-6736(19)30430-1.
- Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011;14(2):145–161. PMID 21412369.
Bibliographic records were retrieved from PubMed. Every reference links to its PubMed record and DOI.